Ans. D. IL-1. (Ref Robbins Basic Pathology 8th/ Table 2-6).IL-1: fever.IL-2: stimulates T cells.IL-3: stimulates bone marrow.IL-4: stimulates IgE production.IL-5: stimulates IgA production.IL-6: stimulates acute-phase protein production.IL-8: recruites Neutrophils. Tumor Necrosis Factor and Interleukin-1# TNF and IL-1 are producedby activated macrophages, as well as mast cells, endothelial cells, and some other cell types.# Their secretion is stimulatedby microbial products, such as bacterial endotoxin, immune complexes, and products of T lymphocytes generated during adaptive immune responses.# The principal role of these cytokines in inflammation is in endothelial activation.# Both TNF and IL-1 stimulate the expression of adhesion molecules on endothelial cells, resulting in increased leukocyte binding and recruitment, and enhance the production of additional cytokines (notably chemokines) and eicosanoids.# TNF also increases the thrombogenicity of endothelium and causes aggregation and activation of neutrophils, and# IL-1 activates tissue fibroblasts, resulting in increased proliferation and production of ECM.- Although TNF and IL-1 are secreted by macrophages and other cells at sites of inflammation, they may enter the circulation and act at distant sites to induce the systemic acute-phase reaction that is often associated with infection and inflammatory diseases.- Components of this reaction include fever, lethargy, hepatic synthesis of various acute-phase proteins, metabolic wasting (cachexia), neutrophil release into the circulation, and release of adrenocorticotropic hormone (inducing corticosteroid synthesis and release). Role of Mediators in Different Reactions of InflammationVasodilationProstaglandins. Nitric oxide, HistamineIncreased vascular permeabilityHistamine and serotonin, C3a and C5a (by liberating vasoactive amines from mast cells, other cells), Bradykinin, Leukotrienes C4, D4, E4, PAF, Substance PLeukocyte recruitment and activationTNF, IL-1, Chemokines, C3a, C5a, Leukotriene B4 (Bacterial products, e.g., N-formyl methyl peptides)Fever0IL-1, TNF, ProstaglandinsPainProstaglandins, Bradykinin, NeuropeptidesTissue damageLysosomal enzymes of leukocytes, Reactive oxygen species, Nitric oxide CytokineCellular sourceTraget cellsBiologic effectsIL-1Monocytes and macrophagesT cells, B cells neuronsCostimulator pyrogenIL-2Tumor cells T cells (TH1)Endothelial cells T cellsB cellsNK cellsGrowthActivation and antibody productionActivation and growthIL-3T cellsImmature hemopoietic stem cellGrowth and differentiationIL-4T cells (TH2)B cellsActivation and growth; isotype switch to IgE; increased MHCII expression T cellsGrowthIL-6Monocytes and macrophages T cells, B cells Ovarian cancer cells Other tumors tumor cellsB cellsT cellsHepatocytesStem cell Autocrine/paracrine growth and viability-enhancing factorDifferentiation, antibody productionCostimulatorInduction of acute-phase responseGrowth and differentiationIL-10T cells (TH2)Monocytes and macrophagesT cells (Th1)Monocytes and macrophagesInhibition of cytokine synthesisInhibition of Ag presentiation and cytokine production B cellsAcivationIL-12MonocytesNK cells, T cells (TH1)InductionIL-13T cells (TH2), mast cells, NK cellsBcells, TH2 cells, macrophagesRegulates IgE secretion by B cell TH2developmentMacrophage activityIL-15Dendritic cells, monocytes, placenta, kidney, lung, heart, TcellsMast cellsNK cell development and functionMast cell proliferation11-16CD4+ and CD8+ T cells, eosinophils, mast cells, dendritic cellsT cells, monocytes, dendritic cells, eosinophilsPrevent antigen-induced T-cell death, chemotactic factor for CD4= T cells, monocytes, eosinophils, dendritic cellsIL-17Acivated CD4+ T cellsT cell, fibrobiastsT-cell activation Induces secretion ofcytokiness by fibroblastsIL-27Monocytes, macrophagesCD4+ T cellsProliferation of naive CD4+ T cells, synergizes with IL-12IFN-YT cells (TH1) NK cellsMonocytes/ macrophagesNK cells, T cells, B cellsActivationAcivation Enhanves responsesTNF-aMonocytes and macrophages T cellsMonokine productionCostimulator pyrogenMonocytes/ macrophages T cells, B cells Neurons Endothelial cells Muscle and fat cellsActivation, inflammationCatabolism/cachexiaAdditional Educational points:# The major cytokines in acute inflammation are TNF and IL-1, as well as a group of chemoattractant cytokines called chemokines. Other cytokines that are more important in chronic inflammation include interferon-? (IFN-?) and IL-12.# Chemokines are classified into four groups based on the arrangement of highly conserved cysteine residues. The two major groups are the CXC and CC chemokines:- CXC chemokines have one amino acid separating the conserved cysteines and act primarily on neutrophils.* IL-8 is typical of this group; it is produced by activated macrophages, endothelial cells, mast cells, and fibroblasts, mainly in response to microbial products and other cytokines such as IL-1 and TNF.- CC chemokines have adjacent cysteine residues and include:* monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1? (MIP-1?) (both chemotactic predominantly for monocytes),* RANTES (regulated on activation normal T expressed and secreted) (chemotactic for memory CD4+ T cells and monocytes), and* eotaxin (chemotactic for eosinophils).