title: Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice.
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).
  
  
  CONCLUSIONS
  This animal study suggests that physiological levels of estrogen, rather than progesterone, enhance immunity and, possibly, protect females from disease symptoms during malaria infection.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205-2179, USA.
authors.forename: Pamela W
authors.initials: PW
authors.lastname: Klein
authors.forename: Judith D
authors.initials: JD
authors.lastname: Easterbrook
authors.forename: Erin N
authors.initials: EN
authors.lastname: Lalime
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001831:Body Temperature; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006400:Hematocrit; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010965:Plasmodium malariae / Q000187:drug effects* / Q000276:immunology; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D011372:Progestins / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D004967:Estrogens; D011372:Progestins; D011374:Progesterone; D004958:Estradiol