Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice. Export

@article{citeulike:4108956, abstract = {BACKGROUND: Previous data from our laboratory suggest that gonadally intact C57BL/6 male mice are more likely than their female counterparts to die from Plasmodium chabaudi infection, to recover more slowly from weight loss and hematocrit loss, and to have reduced interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) responses. Removal of the ovaries, and hence, the primary production of sex steroids in females, reverses these differences. OBJECTIVE: We hypothesized that sex differences in response to P chabaudi may be mediated by differential synthesis of IFN-gamma and IL-10 that is influenced by estrogen, progesterone, or both. METHODS: C57BL/6 female mice (n = 200; n = 10/time point/treatment/experiment) were ovariectomized and implanted with a 21-day controlled-release pellet containing either 0.1 mg of 17beta-estradiol (E(2)), 10 mg of progesterone (P(4)), 0.1 mg of E(2) plus 10 mg of P(4), or cholesterol (placebo). Females were inoculated with 10(6)P chabaudi-infected erythrocytes. Body mass, body temperature, hematocrit, parasitemia, cytokine production, and antibody responses were monitored 0, 3, 5, 7, 10, 14, and 21 days postinoculation. RESULTS: Administration of E(2), either alone or in combination with P(4), mitigated infection-induced weight loss, hematocrit loss, and hypothermia, compared with females receiving placebo pellets (P < 0.05 in each case). Hormone treatment did not affect levels of parasitemia. Females administered E(2) alone or in combination with P(4) produced 4 to 7 times higher IFN-gamma and IL-10 during peak parasitemia than did females implanted with pellets containing either P(4) alone or placebo (P < 0.05 in each case). Exposure to E(2), either alone or in combination with P(4), increased anti-P chabaudi immunoglobulin G (IgG1) responses and the ratio of IgG1 to IgG2c (P < 0.05 in each case). CONCLUSION: This animal study suggests that physiological levels of estrogen, rather than progesterone, enhance immunity and, possibly, protect females from disease symptoms during malaria infection.}, author = {Klein, P. W. and Easterbrook, J. D. and Lalime, E. N. and Klein, S. L.}, citeulike-article-id = {4108956}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.genm.2008.10.001}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19108815}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19108815}, doi = {10.1016/j.genm.2008.10.001}, issn = {1550-8579}, journal = {Gender medicine : official journal of the Partnership for Gender-Specific Medicine at Columbia University}, keywords = {c57bl6, estrogen, female, infection, malaria, mice, progesterone, responses, sex-dependence}, month = {December}, number = {4}, pages = {423--433}, posted-at = {2009-06-15 21:47:18}, priority = {2}, title = {Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice.}, url = {http://dx.doi.org/10.1016/j.genm.2008.10.001}, volume = {5}, year = {2008} }

TY - JOUR ID - citeulike:4108956 L3 - citeulike-article-id:4108956 N2 - BACKGROUND: Previous data from our laboratory suggest that gonadally intact C57BL/6 male mice are more likely than their female counterparts to die from Plasmodium chabaudi infection, to recover more slowly from weight loss and hematocrit loss, and to have reduced interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) responses. Removal of the ovaries, and hence, the primary production of sex steroids in females, reverses these differences. OBJECTIVE: We hypothesized that sex differences in response to P chabaudi may be mediated by differential synthesis of IFN-gamma and IL-10 that is influenced by estrogen, progesterone, or both. METHODS: C57BL/6 female mice (n = 200; n = 10/time point/treatment/experiment) were ovariectomized and implanted with a 21-day controlled-release pellet containing either 0.1 mg of 17beta-estradiol (E(2)), 10 mg of progesterone (P(4)), 0.1 mg of E(2) plus 10 mg of P(4), or cholesterol (placebo). Females were inoculated with 10(6)P chabaudi-infected erythrocytes. Body mass, body temperature, hematocrit, parasitemia, cytokine production, and antibody responses were monitored 0, 3, 5, 7, 10, 14, and 21 days postinoculation. RESULTS: Administration of E(2), either alone or in combination with P(4), mitigated infection-induced weight loss, hematocrit loss, and hypothermia, compared with females receiving placebo pellets (P < 0.05 in each case). Hormone treatment did not affect levels of parasitemia. Females administered E(2) alone or in combination with P(4) produced 4 to 7 times higher IFN-gamma and IL-10 during peak parasitemia than did females implanted with pellets containing either P(4) alone or placebo (P < 0.05 in each case). Exposure to E(2), either alone or in combination with P(4), increased anti-P chabaudi immunoglobulin G (IgG1) responses and the ratio of IgG1 to IgG2c (P < 0.05 in each case). CONCLUSION: This animal study suggests that physiological levels of estrogen, rather than progesterone, enhance immunity and, possibly, protect females from disease symptoms during malaria infection. IS - 4 JF - Gender medicine : official journal of the Partnership for Gender-Specific Medicine at Columbia University SN - 1550-8579 EP - 433 TI - Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice. VL - 5 SP - 423 KW - c57bl6 KW - estrogen KW - female KW - infection KW - malaria KW - mice KW - progesterone KW - responses KW - sex-dependence AU - Klein, PW AU - Easterbrook, JD AU - Lalime, EN AU - Klein, SL PY - 2008/12// UR - http://dx.doi.org/10.1016/j.genm.2008.10.001 ER -