La Flamme A C, MacDonald A S, Pearce E J
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Immunol. 2000 Mar 1;164(5):2419-26. doi: 10.4049/jimmunol.164.5.2419.
The eggs of Schistosoma mansoni are strong inducers of a Th2 response, and previous work has shown that Ag-specific IL-6 is produced within 24 h after the injection of eggs into mice. Investigations to determine the role of IL-6 in orchestrating the early response to schistosome eggs have revealed that IL-12 is rapidly produced in lymph node cell cultures from egg-injected mice. This "early" IL-12 primes for the production of IL-6 and IFN-gamma, for in IL-12-/- mice egg injection fails to stimulate increased production of either of these cytokines. Furthermore, IL-6 also up-regulates IL-10 production which, together with IL-6, negatively regulates IL-12 and IFN-gamma production. Finally, IL-10 down-regulates the production of its inducer, IL-6. These data indicate that the anti-inflammatory role of IL-6 may be effected through negative regulation of type 1 (IFN-gamma) and type 1-associated (IL-12) cytokines either directly (by IL-6) or indirectly (through the induction of IL-10) and suggest that one mechanism by which eggs may support the development of Th2 responses is through the negative regulation of the type 1 response.
曼氏血吸虫卵是Th2反应的强效诱导剂，先前的研究表明，将虫卵注射到小鼠体内后24小时内就会产生抗原特异性白细胞介素-6（IL-6）。为确定IL-6在协调对血吸虫卵早期反应中的作用所开展的研究发现，在注射虫卵的小鼠的淋巴结细胞培养物中会迅速产生白细胞介素-12（IL-12）。这种“早期”IL-12促使IL-6和干扰素-γ（IFN-γ）的产生，因为在IL-12基因敲除小鼠中，注射虫卵无法刺激这两种细胞因子中任何一种的产量增加。此外，IL-6还上调IL-10的产生，IL-10与IL-6一起对IL-12和IFN-γ的产生起负调节作用。最后，IL-10下调其诱导剂IL-6的产生。这些数据表明，IL-6的抗炎作用可能通过直接（由IL-6）或间接（通过诱导IL-10）对1型（IFN-γ）和1型相关（IL-1）细胞因子进行负调节来实现，并提示虫卵支持Th2反应发展的一种机制可能是通过对1型反应的负调节。
