Perimenstrual alterations in type-1/type-2 cytokine balance of normal women

Ann Allergy Asthma Immunol. 1999 Sep;83(3):222-8. doi: 10.1016/S1081-1206(10)62644-0.


Background: Perturbations of the type-1/type-2 cytokine balance play a role in the pathogenesis of many diseases. Several immune-based diseases, such as asthma, have significant clinical exacerbations during specific intervals of the menstrual cycle and are associated with oral contraceptive pills (OCRs). The mechanism for these changes is not known, but may involve alterations in the type-1/type-2 cytokine balance.

Objective: To determine if the type-1/type-2 cytokine balance in healthy women changes during a regular menstrual cycle.

Methods: Peripheral blood mononuclear cells from 14 healthy women (seven taking monophasic OCPs) obtained during the perimenstrual interval (3 days prior to 4 days after the onset of menses) and the mid-cycle interval (days 13 to 16) were stimulated with PHA. Supernatants were analyzed for type-1 (IFN-gamma) and type-2 (IL-10) cytokines.

Results: During the perimenstrual interval PBMC produced less IFN-gamma and more IL-10, resulting in a decreased IFN-gamma: IL-10 ratio compared with the mid-cycle interval. The perimenstrual decrease in the IFN-gamma: IL-10 ratio was observed in women not taking OCP, but not in women taking OCP. Furthermore, the OCP group had a lower mid-cycle IFN-gamma: IL-10 ratio compared with the control group. Finally, subjects reported increased levels of distress during the perimenstrual interval compared with the mid-cycle interval.

Conclusions: These data suggest that healthy women have a perimenstrual shift in the type-1/type-2 cytokine balance toward a type-2 response that is blunted in women taking OCP.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antibody Formation / drug effects
  • Contraceptives, Oral / pharmacology
  • Female
  • Follicular Phase
  • Humans
  • Immunity, Cellular / drug effects
  • Interferon-gamma / immunology
  • Interferon-gamma / physiology*
  • Interleukin-10 / physiology*
  • Interleukin-4 / physiology
  • Interleukin-5 / physiology
  • Interleukins / immunology
  • Interleukins / physiology*
  • Luteal Phase
  • Menstrual Cycle / drug effects
  • Menstrual Cycle / immunology
  • Menstrual Cycle / physiology*
  • Sleep / drug effects
  • Sleep / physiology
  • Surveys and Questionnaires


  • Contraceptives, Oral
  • Interleukin-5
  • Interleukins
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma