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

Pamela W. Klein, Judith D. Easterbrook, Erin N. Lalime, Sabra L. Klein

Research output: Contribution to journalArticle

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-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.

Original languageEnglish (US)
Pages (from-to)423-433
Number of pages11
JournalGender Medicine
Volume5
Issue number4
DOIs
StatePublished - Dec 1 2008

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Keywords

  • estrogen
  • interferon-γ
  • interleukin-10
  • malaria
  • progesterone
  • sex difference
  • sex steroid

ASJC Scopus subject areas

  • Gender Studies

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