INTERLEUKIN-12 ENHANCES CONTACT HYPERSENSITIVITY BY MODULATING THE IN-VIVO CYTOKINE PATTERN IN MICE

It has been proven that interleukin-12 (IL-12) can modify Th1 and Th2 cell-mediated immune diseases by altering the development and cytokine production of the cells, In this study, me investigated the in vivo i mmunomodulatory effect of recombinant murine IL-12 on contact hypersen sitivity, a Th1 cell-mediated disease, For this purpose, Balb/C mice w ere sensitized with 3% 4-ethyoxymethylene-2-phenyl-oxazol-5-one (OXAZ) , and recombinant mouse IL-12 was given simultaneously during the indu ction phase, Contact allergy was then elicited by ear challenge with 1 % OXAZ, We examined the mouse ear smelling response, in vivo cytokine gene expression in the skin and local lymph nodes, and in vitro cytoki ne production by the spleen lymphocytes, It was found that in vivo IL- 12 treatment during the induction phase significantly enhanced the ear swelling response to OXAZ in sensitized mice, Moreover, remarkable mo nonuclear cell infiltration and edema and higher expression of Th1 cyt okine mRNAs (IL-2 and interferon-gamma) in the skin lesion and local l ymph nodes were observed in contact allergic mice with IL-12 treatment compared with contact allergic mice without IL-12 treatment, The expr ession of Th2 cytokine mRNA (IL-4) in the skin lesion and local lymph nodes, however, was largely downregulated, with no change in IL-5 mRNA in IL-12-treated contact allergic mice, We found, unexpectedly, that, similar to the effects on phytohemagglutinin (PHA) stimulated in vitr o IL-2 and IFN-gamma production, PHA-induced in vitro IL-4 production was enhanced in the spleen lymphocytes from IL-12-treated contact alle rgic mice, Our results indicate that exogenous IL-12 enhanced contact hypersensitivity probably because of the in vivo promoting and suppres sing effects of IL-12 on Th1 and Th2 gene expression, respectively.