Acute inflammation

KMU (IPMR)

1. • Egyptian papyrus - 3000 B.C.
• Celsus (Roman in 1st century A.D.)
Rubor - Tumor - Calor - Dolor
redness - swelling - heat - pain
• Virchow added functio laesa later
History

2. What is inflammation?What is inflammation?
Inflammation – Inflammation –
Protective response intended to eliminate the initial Protective response intended to eliminate the initial
cause of cell injury and the necrotic cells and tissues cause of cell injury and the necrotic cells and tissues
arising from the injuryarising from the injury
Inflammation is intimately associated with the Inflammation is intimately associated with the
repair process which includes parenchymal cell repair process which includes parenchymal cell
regeneration and scarringregeneration and scarring

3. Acute - minutes to daysAcute - minutes to days
Characterized by fluid and protein Characterized by fluid and protein
PMN’sPMN’s
Exudate SG > 1.020Exudate SG > 1.020
Chronic - weeks to yearsChronic - weeks to years
Lymphocytes and macrophagesLymphocytes and macrophages
ACUTE Inf - PMN’s (ACUTE Inf - PMN’s (PolyPolymorphonuclear Cells)morphonuclear Cells)
CHRONIC Inf - CHRONIC Inf - MonoMononuclear Cellsnuclear Cells
InflammationInflammation
EXUDATE

4. Acute inflammation
“The immediate and early response to an
injurious agent”
Chronic inflammation
“Inflammation of prolonged duration (weeks
or months) in which active inflammation,
tissue destruction, and attempts at repair are
proceeding simultaneously“

5. Exudate
• ­ vascular permeability
• high protein & cell debris
• SG > 1.020
Transudate
• normal vascular permeability
• hydrostatic pres. ® plasma ultrafiltrate
• low protein (mostly albumin)
• SG < 1.012
Edema
• exudate or transudate ; interstitium or
cavity

6. Acute inflammation Acute inflammation
major componentsmajor components
Transient vasoconstrictionTransient vasoconstriction
VasodilatationVasodilatation
Endothelial permeabilityEndothelial permeability
Extravasation of PMNsExtravasation of PMNs

7. Five classic local signs of acute Five classic local signs of acute
inflammationinflammation
HeatHeat
RednessRedness
SwellingSwelling
PainPain
Loss of functionLoss of function
Calor – vasodilatationCalor – vasodilatation
Rubor – vasodilatationRubor – vasodilatation
Tumor – vascular permeabilityTumor – vascular permeability
Dolor – mediator release/PMNsDolor – mediator release/PMNs
Functio laesa – loss of functionFunctio laesa – loss of function

8. Vascular changes Vascular changes
you need to know thisyou need to know this
Transient vasoconstrictionTransient vasoconstriction
Vasodilation Vasodilation
Exudation of protein rich fluidExudation of protein rich fluid
Blood stasisBlood stasis
MarginationMargination
Emigration/TransmigrationEmigration/Transmigration

9. Vascular changes
Protein exits vessels :
¯ intravascular osmotic
pressure
­ intravascular hydrostatic
pressure
Endothelial gaps at intercellular
junctions:
* immediate transient response
* histamine, bradykinin,
leukotrienes, substance P

11. Vascular permeabilityVascular permeability
Vasodilation – increased blood flowVasodilation – increased blood flow
Increased intravascular hydrostatic pressureIncreased intravascular hydrostatic pressure
Transudate Transudate - ultrafiltrate blood plasma (contains little - ultrafiltrate blood plasma (contains little
protein)protein)
Again, this is very transient and just gets the process started. Again, this is very transient and just gets the process started.
Think acute inflammation, think EXUDATEThink acute inflammation, think EXUDATE
ExudateExudate - (protein-rich with PMNs) - (protein-rich with PMNs)
Exudate is the characteristic fluid of acute inflammationExudate is the characteristic fluid of acute inflammation
Intravascular osmotic pressure decreasesIntravascular osmotic pressure decreases
Osmotic pressure of interstitial fluid increasesOsmotic pressure of interstitial fluid increases
Outflow of water and ions - Outflow of water and ions - edemaedema

13. How do endothelial cellsHow do endothelial cells
become permeable?become permeable?
Endothelial cell contractionEndothelial cell contraction
Junctional retractionJunctional retraction
Direct endothelial injury (immediate sustained Direct endothelial injury (immediate sustained
response) response)
Leukocyte-dependent endothelial injury Leukocyte-dependent endothelial injury
Increased transcytosis of fluidIncreased transcytosis of fluid

14. Direct endothelial injury Direct endothelial injury
(immediate sustained response)(immediate sustained response)
Endothelial cell necrosis and detachmentEndothelial cell necrosis and detachment
Result of severe injury or burnResult of severe injury or burn
Occurs immediately and lasts until vessel Occurs immediately and lasts until vessel
repairedrepaired

15. Occurs at sites of leukocyte accumulationOccurs at sites of leukocyte accumulation
Due to leukocyte activation which releases Due to leukocyte activation which releases
proteolytic enzymes and toxic oxygenproteolytic enzymes and toxic oxygen
Leukocyte-dependent endothelial Leukocyte-dependent endothelial
injuryinjury

16. Leukocyte Cellular EventsLeukocyte Cellular Events
Margination and RollingMargination and Rolling
Adhesion and TransmigrationAdhesion and Transmigration
Migration into interstitial tissueMigration into interstitial tissue

17. SLOWING CONCENTRATION
MarginationRolling Adhesion
Transmigration

19. Selectins CAMS
Integrins
Mucin-like glycoproteins
(Sialyl-Lewis X PSL-1 & ESL-1)
Weak and transient
binding
Results in rolling
Integrins upregulated and activated
for increased affinity to CAMS
Results in firm adhesion

20. MarginationMargination
Normal flow - RBCs and WBCs flow in the Normal flow - RBCs and WBCs flow in the
center of the vesselcenter of the vessel
A A cell poorcell poor plasma is flowing adjacent to plasma is flowing adjacent to
endotheliumendothelium
As blood flow slows, WBCs collect along the As blood flow slows, WBCs collect along the
endothelium endothelium  Margination Margination

21. Endothelial ActivationEndothelial Activation
The underlying stimulus causes release of The underlying stimulus causes release of
mediators which activate the endothelium mediators which activate the endothelium
causing selectins and other mediators to be causing selectins and other mediators to be
moved quickly to the surfacemoved quickly to the surface

22. Selectins Selectins
Selectins bind selected sugars Selectins bind selected sugars
SeSelected + lected + LectinsLectins (sugars) = Selectins (sugars) = Selectins
Some selectins are present on endothelial cells (E-Selectin)Some selectins are present on endothelial cells (E-Selectin)
Some selectins are present on leukocytes (L-Selectin)Some selectins are present on leukocytes (L-Selectin)
Some selectins are present on platelets (P-Selectin)Some selectins are present on platelets (P-Selectin)
Weak & transient bindingWeak & transient binding
Results in Results in rollingrolling

23. Fig 3-9Fig 3-9

24. RollingRolling
Selectins transiently bind to receptorsSelectins transiently bind to receptors
PMNs bounce or roll along PMNs bounce or roll along  Rolling Rolling

26. AdhesionAdhesion
Mediated by integrins ICAM-1 and VCAM-1 Mediated by integrins ICAM-1 and VCAM-1

28. TransmigrationTransmigration
Mediated/assisted by PECAM-1 & ICAM-1 (Integrins)Mediated/assisted by PECAM-1 & ICAM-1 (Integrins)
Diapedesis (cells crawling)Diapedesis (cells crawling)
Primary in venulesPrimary in venules
Collagenases degrade BM Collagenases degrade BM ­­ PermeabilityPermeability

30. ChemotaxisChemotaxis
Movement toward the site of injury along a Movement toward the site of injury along a
chemical gradientchemical gradient
Chemotactic factors includeChemotactic factors include
Complement components (20 serum proteins)Complement components (20 serum proteins)
Arachadonic acid (AA) metabolitesArachadonic acid (AA) metabolites
Soluble bacterial productsSoluble bacterial products
Chemokines, cytokinesChemokines, cytokines

31. Phagocytosis & DegranulationPhagocytosis & Degranulation
Phagocytosis (engulf and destroy)Phagocytosis (engulf and destroy)
Degranulation and the oxidative burst destroy Degranulation and the oxidative burst destroy
the engulfed particlethe engulfed particle
Recognition & attachmentRecognition & attachment
Opsonins coat target and bind to leukocytesOpsonins coat target and bind to leukocytes
EngulfmentEngulfment
Killing/degradationKilling/degradation
OO
22 dep: Reactive O dep: Reactive O
22 species in lysosomes & EC species in lysosomes & EC
OO
2 2 indep: Bactericidal permeability agents, indep: Bactericidal permeability agents,
lysozyme, MBP, lactoferrinlysozyme, MBP, lactoferrin

32. Leukocyte-induced tissue Leukocyte-induced tissue
injuryinjury
Lysosomal enzymes are released into the Lysosomal enzymes are released into the
extracellular space during phagocytosis causing extracellular space during phagocytosis causing
cell injury and matrix degradationcell injury and matrix degradation
Activated leukocytes release reactive oxygen Activated leukocytes release reactive oxygen
species and products of arachidonic acid species and products of arachidonic acid
metabolism which can injure tissue and metabolism which can injure tissue and
endothelial cellsendothelial cells
These events underlie many human diseases (e.g. These events underlie many human diseases (e.g.
Rheumatoid arthritis)Rheumatoid arthritis)

33. Table 3-3Table 3-3
GeneticGenetic DefectDefect
LAD 1LAD 1 B chain of CD11/CD18 integrinsB chain of CD11/CD18 integrins
LAD 2LAD 2 Sialylated oligosaccharideSialylated oligosaccharide
Neutrophil-specific granule Neutrophil-specific granule
deficiencydeficiency
Absence of neutrophil-specific Absence of neutrophil-specific
granules granules
CGDCGD
X-linkedX-linked
ARAR
Defective chemotaxisDefective chemotaxis
NADPH oxidatise (membrane)NADPH oxidatise (membrane)
NADPH oxidase (cytoplasm)NADPH oxidase (cytoplasm)
MPO deficiencyMPO deficiency Absent MPO-H2O2 systemAbsent MPO-H2O2 system
Chediak-Higashi syndromeChediak-Higashi syndrome Lysosomal defectLysosomal defect
AcquiredAcquired
Thermal injury, DM, CA, sepsisThermal injury, DM, CA, sepsisChemotaxisChemotaxis
Dialysis, DMDialysis, DM AdhesionAdhesion
Leukemia, anemia, sepsis, DM, Leukemia, anemia, sepsis, DM,
neonates, malnutritionneonates, malnutrition
Phagocytosis & microbicidal Phagocytosis & microbicidal
activityactivity

34. Leukocyte adhesion deficiency 1 Leukocyte adhesion deficiency 1
(LAD-1)(LAD-1)
Recurrent bacterial infectionsRecurrent bacterial infections
Inflammatory lesions lack neutrophil infiltrateInflammatory lesions lack neutrophil infiltrate
High numbers of neutrophils in the circulationHigh numbers of neutrophils in the circulation
Neutrophils from patients can roll but do not stickNeutrophils from patients can roll but do not stick
BB chain of CD11/CD18 integrinchain of CD11/CD18 integrin
Transfuse patients with normal neutrophils and they Transfuse patients with normal neutrophils and they
can emigratecan emigrate

35. Mechanism of leukocyte Mechanism of leukocyte
adhesion deficiency 1 (LAD -1)adhesion deficiency 1 (LAD -1)
Absence of integrins on neutrophilsAbsence of integrins on neutrophils
Mutation in n-terminal region of the integrin Mutation in n-terminal region of the integrin bb chain chain
inhibits proper integrin assemblyinhibits proper integrin assembly
Normal function is restored following transfection of Normal function is restored following transfection of
patient cells with cDNA for patient cells with cDNA for bb chain chain

36. Chediak-Higashi SyndromeChediak-Higashi Syndrome
This syndrome has been on every board test since This syndrome has been on every board test since
NoahNoah
Defect in chemotaxis and lysosomal degranulation Defect in chemotaxis and lysosomal degranulation
into phagosomes into phagosomes

38. Chronic Granulomatous DiseaseChronic Granulomatous Disease
Defect in NADPH oxidase systemDefect in NADPH oxidase system
Marked decrease in ability to kill microorganismsMarked decrease in ability to kill microorganisms

39. Chemical mediators of inflammationChemical mediators of inflammation
Plasma-derived Plasma-derived
Circulating precursors Circulating precursors
Have to be activatedHave to be activated
Cell-derivedCell-derived
Sequestered intracellular Sequestered intracellular
Synthesized de novoSynthesized de novo
Most mediators bind to receptors on cell surface but Most mediators bind to receptors on cell surface but
some have direct enzymatic or toxic activitysome have direct enzymatic or toxic activity
Mediators are tightly regulatedMediators are tightly regulated

41. Chemotactic
factors (eg. c5a)
Chemotactic
factors (eg. c5a)
Tissue
injury
Tissue
injury
Vasoactive
mediators
(eg. histamine)
Vasoactive
mediators
(eg. histamine)
Increased vascular
permeability
Increased vascular
permeability
Recruitment of inflammatory
cells
Recruitment of inflammatory
cells
EdemaEdema PMNsPMNs MonosMonos
Production of
inflammatory
mediators
Production of
inflammatory
mediators
Acute
inflammation
Acute
inflammation
Chronic
inflammation
Chronic
inflammation

42. Plasma Mediator Systems - Interaction
 
1.   Kinin
2.   Clotting
3.   Complement
4.   Fibrinolytic 

43. C5
C5
a
Plasminogen  ®  Plasmin
C3
C3a
   Fibrin   ®  FSPs
Prothrombin ® Thrombin
Fibrinogen 
XII
Kinin
Complement
Clotting
Fibrinolytic
Fibrinopeptides
Prekallikrein
XIIa 
Kallikrein
 High Mol. Wt. Kininogen Bradykinin

Plasma Mediator Systems - Interaction

45. Kinin cascadeKinin cascade
Leads to formation of bradykininLeads to formation of bradykinin
Bradykinin causes Bradykinin causes
Increased vascular permeabilityIncreased vascular permeability
Arteriolar dilatation Arteriolar dilatation
Smooth muscle contraction Smooth muscle contraction
Bradykinin is short lived (kininases)Bradykinin is short lived (kininases)
Vascular actions similar to histamineVascular actions similar to histamine

46. Complement systemComplement system
Role in immunity (C5-9 complex)Role in immunity (C5-9 complex)
Membrane Attack Complex (MAC C5-9)Membrane Attack Complex (MAC C5-9)
Punches a hole in the membranePunches a hole in the membrane

47. Complement systemComplement system
Role in inflammation (c3a and c5a)Role in inflammation (c3a and c5a)
Vascular effectsVascular effects
Increase vascular permeability and vasodilationIncrease vascular permeability and vasodilation
Similar to histamineSimilar to histamine
Activates lipoxygenase pathway of arachidonic acid Activates lipoxygenase pathway of arachidonic acid
metabolism (c5a)metabolism (c5a)

48. Complement systemComplement system
Leukocyte activation, adhesion and chemotaxis (c5a)Leukocyte activation, adhesion and chemotaxis (c5a)
PhagocytosisPhagocytosis
c3b acts as opsonin and promotes phagocytosis by cells c3b acts as opsonin and promotes phagocytosis by cells
bearing receptors for c3bbearing receptors for c3b

49. Inflammatory Mediators from Inflammatory Mediators from
ComplementComplement
AnaphylatoxinsAnaphylatoxins::
C3a, C5a, & C4aC3a, C5a, & C4a trigger mast cells to release histamine trigger mast cells to release histamine
and cause vasodilatationand cause vasodilatation
C5aC5a also activates the lipoxygenase system in PMNs also activates the lipoxygenase system in PMNs
and monocytes and monocytes ®® release of inflammatory release of inflammatory
mediatorsmediators
Leukocyte activation, adhesion, & chemotaxisLeukocyte activation, adhesion, & chemotaxis::
C5aC5a activates leukocytes, promotes leukocyte binding activates leukocytes, promotes leukocyte binding
to endothelium via integrins and is chemotactic for to endothelium via integrins and is chemotactic for
PMNs, monos, eos, & basosPMNs, monos, eos, & basos

50. Inflammatory Mediators from Inflammatory Mediators from
ComplementComplement
PhagocytosisPhagocytosis::
C3b and C3biC3b and C3bi are opsonins are opsonins
ControlControl: :
Convertases are destabilized by "decay accelerating Convertases are destabilized by "decay accelerating
factor" (DAF) factor" (DAF)
Inability to express DAF causes Inability to express DAF causes paroxysmal nocturnal paroxysmal nocturnal
hemoglobinuriahemoglobinuria
C1 inhibitor (C1INH) deficiency causes C1 inhibitor (C1INH) deficiency causes hereditary hereditary
angioneurotic edemaangioneurotic edema

52. Vasoactive aminesVasoactive amines
HistamineHistamine
Found in mast cells, basophils and plateletsFound in mast cells, basophils and platelets
Released in response to stimuli Released in response to stimuli
Promotes arteriolar dilation and venular Promotes arteriolar dilation and venular
endothelial contraction endothelial contraction
 results in widening of interendothelial cell junctions results in widening of interendothelial cell junctions
with increased vascular permeabilitywith increased vascular permeability
SerotoninSerotonin
Vasoactive effects similar to histamineVasoactive effects similar to histamine
Found in platelets Found in platelets
Released when platelets aggregateReleased when platelets aggregate

53. Bradykinin: Potent biomolecule 
1. Vasodilatation
2. Increased vascular permeability
3. Contraction of smooth muscle
4. Pain on injection
5. Short life, kininase degrades 
Bradykinin: Potent biomolecule 
1. Vasodilatation
2. Increased vascular permeability
3. Contraction of smooth muscle
4. Pain on injection
5. Short life, kininase degrades 
Factor XII activated by:
1. Plasmin
2. Kallikrein
3. Collagen & basement membrane
4. Activated platelets
5. Co-factor = HMWK
Factor XII activated by:
1. Plasmin
2. Kallikrein
3. Collagen & basement membrane
4. Activated platelets
5. Co-factor = HMWK
­ Vascular Permeability:
- Bradykinin
- Fibrionopeptides
- Fibrin Split Prod.
- Factor Xa
- Leukotrienes
­ Vascular Permeability:
- Bradykinin
- Fibrionopeptides
- Fibrin Split Prod.
- Factor Xa
- Leukotrienes

54. Arachidonic Acid (AA)Arachidonic Acid (AA)
Where is it located?Where is it located?
AA is a component of cell membrane phospholipidsAA is a component of cell membrane phospholipids
The breakdown of AA into its metabolites The breakdown of AA into its metabolites
produces a variety of biologic effectsproduces a variety of biologic effects

55. Arachidonic acid metabolitesArachidonic acid metabolites
Metabolites of AA - short-range hormonesMetabolites of AA - short-range hormones
AA metabolites act locally at site of generationAA metabolites act locally at site of generation
Rapidly decay or are destroyedRapidly decay or are destroyed

56. Arachidonic AcidArachidonic Acid
AA is released from the cell membrane by AA is released from the cell membrane by
phospholipasesphospholipases which have themselves been which have themselves been
activated by various stimuli and/or activated by various stimuli and/or
inflammatory mediatorsinflammatory mediators
AA metabolism occurs via two major pathways AA metabolism occurs via two major pathways
named for the enzymes that initiate the named for the enzymes that initiate the
reactions; reactions; lipoxygenaselipoxygenase and and cyclooxygenasecyclooxygenase

57. AA metabolites (eicosanoids)
Cyclooxygenases synthesize
Prostaglandins
Thromboxanes
Lipoxygenases synthesize
Leukotrienes
Lipoxins

59. PGG
2
¯
PGH
2
PGI
2
Prostacyclin
TXA
2
Thromboxane
PGD
2
; PGE
2

PGF
2

Vasodilatation
Inhibits Platelet Aggregation
Vasoconstriction
Promotes Platelet Aggregation
Vasodilatation
Edema
PGI
2
TXA
2

60. Arachidonic Acid PathwaysArachidonic Acid Pathways
you need to know thisyou need to know this
LipoxygenaseLipoxygenase
5-HETE5-HETE
ChemotaxisChemotaxis
5-HPETE5-HPETE
Leukotriene generationLeukotriene generation
LeukotrienesLeukotrienes
VasoconstricitonVasoconstriciton
BronchospasmBronchospasm
Increased vascular Increased vascular
permeabilitypermeability
LipoxygenaseLipoxygenase
5-HETE5-HETE
ChemotaxisChemotaxis
5-HPETE5-HPETE
Leukotriene generationLeukotriene generation
LeukotrienesLeukotrienes
VasoconstricitonVasoconstriciton
BronchospasmBronchospasm
Increased vascular Increased vascular
permeabilitypermeability
CyclooxygenaseCyclooxygenase
ProstaglandinsProstaglandins
VasodilatationVasodilatation
Increased vascular Increased vascular
permeabilitypermeability
ProstacyclinProstacyclin
VasodilatationVasodilatation
Inhibits platlelet aggregationInhibits platlelet aggregation
Thromboxane A2Thromboxane A2
VasoconstrictionVasoconstriction
Promotes platlelet aggregationPromotes platlelet aggregation
CyclooxygenaseCyclooxygenase
ProstaglandinsProstaglandins
VasodilatationVasodilatation
Increased vascular Increased vascular
permeabilitypermeability
ProstacyclinProstacyclin
VasodilatationVasodilatation
Inhibits platlelet aggregationInhibits platlelet aggregation
Thromboxane A2Thromboxane A2
VasoconstrictionVasoconstriction
Promotes platlelet aggregationPromotes platlelet aggregation

61. Arachidonic Acid PathwaysArachidonic Acid Pathways
you need to know thisyou need to know this
LipoxygenaseLipoxygenase
5-HETE, 5-HPETE, 5-HETE, 5-HPETE,
LeukotrienesLeukotrienes
Spasm (Vaso, Broncho)Spasm (Vaso, Broncho)
LipoxygenaseLipoxygenase
5-HETE, 5-HPETE, 5-HETE, 5-HPETE,
LeukotrienesLeukotrienes
Spasm (Vaso, Broncho)Spasm (Vaso, Broncho)
CyclooxygenaseCyclooxygenase
Prostaglandins - EDEMAProstaglandins - EDEMA
Prostacyclin vs TXA2Prostacyclin vs TXA2
Vasodilatation vs. Vasodilatation vs.
VasoconstrictionVasoconstriction
Platelet aggregationPlatelet aggregation
Inhibits vs. promotesInhibits vs. promotes
CyclooxygenaseCyclooxygenase
Prostaglandins - EDEMAProstaglandins - EDEMA
Prostacyclin vs TXA2Prostacyclin vs TXA2
Vasodilatation vs. Vasodilatation vs.
VasoconstrictionVasoconstriction
Platelet aggregationPlatelet aggregation
Inhibits vs. promotesInhibits vs. promotes

62. Arachidonic Acid MetabolitesArachidonic Acid Metabolites
Participate in every aspect of acute inflammationParticipate in every aspect of acute inflammation
Effective Anti-inflammatory agents act on AA pathwaysEffective Anti-inflammatory agents act on AA pathways
Aspirin and Non-Steroidal Anti-inflammatory Drugs Aspirin and Non-Steroidal Anti-inflammatory Drugs
(NSAID’s) - Cyclooxygenase path(NSAID’s) - Cyclooxygenase path
Steroids act, in part, by inhibiting Phospholipase A2Steroids act, in part, by inhibiting Phospholipase A2

63. Platelet-Activating Factor Platelet-Activating Factor
(PAF)(PAF)
Another phospholipid-derived mediator released by Another phospholipid-derived mediator released by
phospholipasesphospholipases
Induces aggregation of plateletsInduces aggregation of platelets
Causes vasoconstriction and bronchoconstrictionCauses vasoconstriction and bronchoconstriction
100 to 1,000 times more potent than histamine in 100 to 1,000 times more potent than histamine in
inducing vasodilation and vascular permeabilityinducing vasodilation and vascular permeability
Enhances leukocyte adhesion, chemotaxis, Enhances leukocyte adhesion, chemotaxis,
degranulation and the oxidative burstdegranulation and the oxidative burst
It does everything!It does everything!

64. CytokinesCytokines
Polypeptides that are secreted by cellsPolypeptides that are secreted by cells
Act to regulate cell behaviorsAct to regulate cell behaviors
Autocrine, paracrine or endocrine effectsAutocrine, paracrine or endocrine effects
These “biological response modifiers” are being These “biological response modifiers” are being
actively investigated for therapeutic use in actively investigated for therapeutic use in
controlling the inflammatory response.controlling the inflammatory response.

65. 1. Macrophages make IL-1 & TNF-a
2. T-cells make TNF-b (lymphotoxin)
3. Can be autocrine, paracrine, endocrine
4. IL-1, TNF, IL-6  acute phase responses,
fever, (appetite, slow wave sleep, ­ circ.
pmn,­ ACTH, ­ corticosteroids)
5.TNF notable for role in septic shock and
maintenance of body mass (cachexia in cancer
from ­ ­ TNF-a )
Lymphocyte function

67. Selected Inflammatory Cells & Selected Inflammatory Cells &
Their ChemokinesTheir Chemokines
Target CellTarget CellImportant ChemokinesImportant Chemokines
NeutrophilsNeutrophilsIL-8, GroIL-8, Groaa, , bb, , gg, others, others
MonocytesMonocytes MIP-1MIP-1aa, MIP-1, MIP-1bb, MCP-1,2,3, MCP-1,2,3
EosinophilsEosinophilsEotaxinEotaxin
LymphocytesLymphocytesLymphotaxinLymphotaxin
BasophilsBasophils IL-8, MIP-1IL-8, MIP-1aa, MCP-1,3, RANTES, MCP-1,3, RANTES

68. Nitric OxideNitric Oxide
NO is a soluble free radical gasNO is a soluble free radical gas
Made by nitric oxide synthetase (NOS) in Made by nitric oxide synthetase (NOS) in
endothelium (eNOS), macrophages (iNOS), endothelium (eNOS), macrophages (iNOS),
and specific neurons in the brain (nNOS)and specific neurons in the brain (nNOS)
Broad range of functions and effects that are Broad range of functions and effects that are
short rangeshort range
Vasodilatation by relaxing smooth muscle.Vasodilatation by relaxing smooth muscle.
¯¯ platelet aggregationplatelet aggregation
Inhibits mast cellsInhibits mast cells
Regulates leukocyte recruitmentRegulates leukocyte recruitment

69. Outcomes of Acute InflammationOutcomes of Acute Inflammation
ResolutionResolution
FibrosisFibrosis
Abscess formationAbscess formation
Progression to chronic inflammationProgression to chronic inflammation