Sex steroids and the immune system

Abstract

Immunology in its inception was believed to be a science dealing solely with the defense of the body against infections. The Oxford dictionary defined immunology as ‘‘the study of resistance to infection in man and animals’’ [1]. Since then, there has been an immense growth in immunology. This growth has resulted in increased awareness of the role of the immune system in disease states, such as allergic, autoimmune, and cardiovascular diseases, and its interactions with other systems of the body. An interaction between the immune system and reproductive hormones was observed as early as the 19th century. In 1898, Calzoari described the changes in the thymus following castration [2]. At that time, the thymus was believed to have no functional importance, and his observations failed to capture the attention of scientists. Much later, clinicians noted a higher prevalence of autoimmune diseases in women. Despite this evidence of sex hormonal involvement in autoimmune diseases, there were no studies addressing this issue. In 1972, a report by the National Advisory Committee on the Future of Arthritis Research sponsored by the Arthritis Foundation urged that ‘‘an explanation be sought for the remarkable female to male ratio in systemic lupus’’ [1]. A significant body of data establishes that immune responsiveness differs between men and women and that gonadal steroids are involved intimately in this immunologic dimorphism. Because autoimmune diseases result from the perturbation of normal immune function, autoimmunity also demonstrates a dimorphic pattern. This article examines the effects of sex steroids on the immune system. The sexual dimorphism that is observed in normal immune response and in susceptibility to infections and autoimmune disorders is reviewed. The effects of individual sex steroids on different aspects of the immune function are summarized.