Effects of Sex Hormones on Some T and B Cell Functions, Evidenced by Differential Immune Expression Between Male and Female Mice and Cyclic Pattern of Immune Responsiveness During the Estrous Cycle in Female Mice*

Abstract

The responses of spleen cells from male and female BALB/c mice were evaluated to determine if sex-related variations in immune expression could be found. The immunologic assays used included blastogenic responses to mitogens, and direct and indirect measurement of plaque-forming cells against particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Newborn mice did not demonstrate the sex-associated immune differences; and among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed. The blastogenic responsiveness of spleens from female BALB/c was greater at proestrus and metestrus, as compared to estrus and diestrus. The peaks of responsiveness corresponded to reported elevated levels of estrogen and pregnenolone during these phases of the cycle. Similar results were obtained with the IgM plaque-forming cell responses, which were also increased at proestrus and metestrus. This study supports a role of sex hormones in modulation of immune expression.

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

“…In rodents, E2 levels are lowest during estrus and metestrus, gradually increasing during diestrus, and reaching a peak at proestrus stage (63). It has been demonstrated that female hormones, E2 and prolactin, modulate immune responsiveness in adult mice and that the proestrus state of the estrus cycle is characterized by a more vigorous immune response compared with the diestrus state (64)(65)(66)(67). The observed restoration of organ function following trauma-hemorrhage after flutamide administration was also found to be estrogen-mediated, owing to increases in estrogen levels by increasing the conversion of testosterone to estrogen (68).…”

Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats

“…Although there is no direct evidence for this, there is considerable evidence demonstrating that circulating sex hormones do modulate immune responses (28,29,61), and estrogens and progesterone have been found to influence IL-1 release from monocytes (55). Indeed, cytokine release from immune cells was found to vary in premenopausal women, depending on the stage in the menstrual cycle (10,27,55,63).…”

Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17β-estradiol

“…Estrogen modulation of the immune system is not restricted to pregnancy alone, because its role is also documented in many autoimmune disorders and in the outcome after TH (7,14,17,18,23,55). The majority of the estrogen effects are mediated by two distinct intracellular receptors, ER-␣ and ER-␤, each encoded by unique genes (14,20,34). However, studies have also suggested that E2 interacts with other cell surface receptors including growth factor or dopamine receptors (13,19,30,47).…”

“…Because 17␤-estradiol is able to regulate cytokine genes, and the splenic T lymphocyte cytokine releases is altered after TH, continued synthesis of 17␤-estradiol in proestrus females appears to be responsible for the maintenance of T lymphocyte cytokine release associated with the protection of immune functions after TH. inflammation; immune suppression; steroid synthesis; T lymphocytes; cytokines THE INFLUENCE OF GENDER on immune functions has been recognized for many years, and in general, women are known to develop enhanced humoral responses compared with men and are more prone to autoimmune diseases (9,12,20). Trauma-hemorrhage and resuscitation (TH) produce severe impairment of both immune and cardiovascular functions (51,56,57).…”