Anti-inflammatory action of IL-4. Negative regulation of contact sensitivity to trinitrochlorobenzene.
We examined the effects of IL-4, a cytokine produced by Th2 cells, on the development of an Ag-specific, T cell-mediated inflammatory response in a hapten-induced model of contact sensitivity (CS). Intravenous administration of IL-4 was ineffective in modulating the development of CS when administered on days 0, 1, and 2 after sensitization with the hapten trinitrochlorobenzene. In contrast, such treatment significantly reduced the response when given on the day of challenge. Conversely, treatment with anti-IL-4 mAb on day 4 markedly increased the magnitude of CS but was without effect when administered on days 0, 1, and 2. These results suggest that IL-4 interferes with CS at the efferent but not the afferent limb of the response. IL-4 had no inhibitory effect on the ability of immune lymph node cells to transfer adoptively CS or their proliferation upon restimulation with hapten. However, the expression of CS by immune cells was severely curtailed in mice treated with IL-4 prior to immune cell transfer. Furthermore, IL-4 inhibited monokine (gamma-IFN inducible protein [IP-10] and TNF-alpha) expression in macrophages induced by treatment with culture supernatants from the Ag-stimulated immune lymph node cells. These results indicate that suppression of Ag-specific inflammatory CS response by IL-4 may be mediated at least in part through inhibition of cytokine production by mononuclear phagocytes infiltrating the site.
Gautam
S C
SC
Research Institute, Cleveland Clinic Foundation, OH 44195.
Chikkala
N F
NF
Hamilton
T A
TA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000517:prevention & control*; D005260:Female; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D015846:Monokines / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014301:Trinitrobenzenes / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015846:Monokines; D012333:RNA, Messenger; D014301:Trinitrobenzenes; D015847:Interleukin-4