Leishmania major-infected C3H mice treated with anti-IL-12 mAb develop but do not maintain a Th2 response.
Leishmania major-infected C3H mice develop a Th1 response, but studies have shown that treatment of C3H mice with anti-IL-12 or anti-IFN-gamma mAb promotes the development of a Th2 response and susceptibility. However, we discovered that C3H mice treated for 3 wk with either anti-IL-12 or anti-IFN-gamma mAb eventually resolved their lesions and switched from a Th2 to a Th1 response. No significant differences in IL-4, IL-10, or IFN-gamma levels or in the parasite burden could be detected between BALB/c and anti-IL-12-treated C3H mice early after infection, suggesting that the instability of the Th2 response in anti-IL-12-treated C3H mice was unrelated to levels of these cytokines and parasite numbers. However, anti-IL-12-treated C3H mice continued to produce IL-12 in spite of exhibiting a Th2 phenotype. To determine whether the production of IL-12 was associated with the healing observed in these animals, we treated C3H mice with anti-IL-12 continuously for 12 wk. In contrast to C3H mice given anti-IL-12 for 3 wk, C3H mice continuously treated with anti-IL-12 failed to heal. These results suggest that qualitative differences in Th2-type responses may influence their stability and that the presence of IL-4, IL-10, or high parasite numbers is not sufficient to maintain a Th2 response in mice with certain genetic backgrounds.
Hondowicz
B D
BD
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia 19104, USA.
Scharton-Kersten
T M
TM
Jones
D E
DE
Scott
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018664:Interleukin-12; D007371:Interferon-gamma