Experimental Parasitology 96, 121–129 (2000) doi:10.1006/expr.2000.4572, available online at http://www.idealibrary.com on Possible Modulation by Male Sex Hormone of Th1/Th2 Function in Protection against Plasmodium chabaudi chabaudi AS Infection in Mice Zhi-Hui Zhang, 1 Lin Chen, 1 Susumu Saito, Osami Kanagawa,* and Fujiro Sendo Department of Immunology and Parasitology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan; and *Department of Pathology, Washington University School of Medicine, Washington University Medical Center, Campus Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110-1093 Zhang, Z.-H., Chen, L., Saito, S., Kanagawa, O., and Sendo, F. INTRODUCTION 2000. Possible modulation by male sex hormone of Th1/Th2 function in protection against Plasmodium chabaudi chabaudi AS infection in mice. Experimental Parasitology 96, 121–129. We examined the The mechanisms of host-mediated protection against ma- mortality, survival time, and parasitemia in interferon  receptor (IFN- larial infection must be clarified to develop effective vac-  R)-deficient (IFN- R -/- ) and IL-4-deficient (IL-4 -/- ) mice infected cines. To this end, numerous studies have been performed, with Plasmodium chabaudi AS and compared them with the wild type and a consensus has been reached that both Th1 and Th2 counterparts (IFN- R +/+ and IL-4 +/+ , respectively). (1) Mortality was responses may be required for complete protection against higher and survival time was shorter in males of both IFN- R -/- and this parasite. These recent investigations have generally used IL-4 -/- mice infected with P. chabaudi AS, compared with their wild mice infected with Plasmodium chabaudi AS (Langhoore type counterparts, whereas such a difference was not observed in et al. 1989; Langhorne et al. 1989; Podoba and Stevenson female mice. (2) These differences between males and females were 1991; Taylor et al. 1993, 1994). IFN- produced mainly by not observed when male mice were castrated; however, female castra- tion had no effect on the data. (3) The rate of parasitemia in both male Th1 cells inhibits parasitemia in P. chabaudi infection (Clark and female IFN- R -/- and IL-4 -/- mice was higher at some points et al. 1987; Stevenson et al. 1990), protects against lethal during the observation than in the wild type counterparts. (4) These infection by Plasmodium yoelii (Shear et al. 1989), and results on susceptibility vs resistance to P. chabaudi AS infection can inhibits the liver stage of P. yoelii infection (Ferreira et al. be explained partially by the levels of expression of Th1/Th2 cytokine 1986). This cytokine is also involved in the induction of and chemokine mRNAs in the spleen cells of the infected mice. These protective immunity against challenge with viable sporozo- results suggest that male sex hormones modulate the function of Th1/ ites (Schmitt et al. 1991; Tsuji et al. 1995). On the other Th2 cells and that these T cells counteract the activity of these hormones hand, it has been demonstrated that B cells are necessary in protection against P. chabaudi AS infection in mice.  2000 Aca- for protective immunity against P. chabaudi AS (Meding demic Press and Langhorne 1991; von der Weid et al. 1994; Rosa et al. Index Descriptors and Abbreviations: Plasmodium chabaudi cha- baudi AS; Th1/Th2 function; male sex hormone; IFN- R -/- , interferon 1999; Langhorne et al. 1998), and IgG1 is involved in the gamma receptor gene deficient; IL-4 -/- , interleukin-4 gene deficient; protection against P. chabaudi AS in mice transferred with PRBC, parasitized red blood cells. a specific Th2 cell clone (Taylor et al. 1993). This class of immunoglobulin is dependent on Th2-derived cytokine, IL- 4 (Mosmann et al. 1989). To systematically elucidate the mechanisms involved in 1 Zhi-Hui Zhang and Lin Chen contributed equally to the work. protection against malaria infection, we compared mortality, 0014-4894/00 $35.00 121 Copyright  2000 by Academic Press All rights of reproduction in any form reserved.