TY - JOUR
T1 - Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice
AU - Klein, Pamela W.
AU - Easterbrook, Judith D.
AU - Lalime, Erin N.
AU - Klein, Sabra L.
N1 - Funding Information:
The authors thank Jenifer Kaplan for technical assistance. Financial support for this study was provided by the Johns Hopkins Malaria Research Institute and National Institutes of Health grant ROI AIOS499S.
PY - 2008/12
Y1 - 2008/12
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-γ (IFN-γ) 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-γ 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 17β-estradiol (E2), 10 mg of progesterone (P4), 0.1 mg of E2 plus 10 mg of P4, or cholesterol (placebo). Females were inoculated with 106P 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 E2, either alone or in combination with P4, 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 E2 alone or in combination with P4 produced 4 to 7 times higher IFN-γ and IL-10 during peak parasitemia than did females implanted with pellets containing either P4 alone or placebo (P < 0.05 in each case). Exposure to E2, either alone or in combination with P4, 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.
AB - 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-γ (IFN-γ) 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-γ 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 17β-estradiol (E2), 10 mg of progesterone (P4), 0.1 mg of E2 plus 10 mg of P4, or cholesterol (placebo). Females were inoculated with 106P 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 E2, either alone or in combination with P4, 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 E2 alone or in combination with P4 produced 4 to 7 times higher IFN-γ and IL-10 during peak parasitemia than did females implanted with pellets containing either P4 alone or placebo (P < 0.05 in each case). Exposure to E2, either alone or in combination with P4, 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.
KW - estrogen
KW - interferon-γ
KW - interleukin-10
KW - malaria
KW - progesterone
KW - sex difference
KW - sex steroid
UR - http://www.scopus.com/inward/record.url?scp=57649205323&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57649205323&partnerID=8YFLogxK
U2 - 10.1016/j.genm.2008.10.001
DO - 10.1016/j.genm.2008.10.001
M3 - Article
C2 - 19108815
AN - SCOPUS:57649205323
SN - 1550-8579
VL - 5
SP - 423
EP - 433
JO - Gender Medicine
JF - Gender Medicine
IS - 4
ER -