Pregnancy and Postpartum Influences on Rheumatoid Arthritis Activity: Nature's Model to Investigate Systemic Biological Mechanisms in the Disease

The hormonal, immunological, and microvascular endothelial (MVE) systems are believed to be important determinants of RA. These core systems interactions may influence clinical activity of this disease during pregnancy and postpartum. Notably, immunological adaptations have been documented during these periods of tightly programmed physiological changes. The neuroendocrine immune (NEI) systems of hormones and cytokines act in counter-regulatory networks and cascades. Hormones modulate immunological reactivity, and the NEI interactions complexly affect synovial and MVE target tissues. Such local joint effects may not be reflected well by cytokine or hormonal blood levels. Additionally, peripheral blood mononuclear cell cultures can provide valuable information on immunological activation. Cytokines and hormones interact as components of the complex multifactorial networks operating in the in vivo biological model. The highly programmed physiology of pregnancy and postpartum offers insights and examples of NEI and MVE relations, as they may influence clinical activity of RA. New dynamic concepts of immunological reactivity are reviewed in relation to contextual modulation during pregnancy and postpartum. The concept of type1/type2 cytokine shift also provides a framework for interpreting immunological mechanisms and their respective interactions during pregnancy and postpartum. Deciphering interactive dynamics of these systems promises to reveal basic mechanisms of how pregnancy ameliorates some diseases like RA, but may worsen others like SLE. Risks of developing premenopausal onset RA are also inextricably linked to the biology of NEI and MVE systems interactions. Endorsing multisystems interactions during pregnancy and postpartum, the concluding section proposes resource protocols and models for future multidisciplinary investigations on fundamental mechanisms influencing the RA activity. Nature's model of pregnancy and postpartum influences on activity of RA may offer the best opportunity to study integrative biology of this profoundly complex disease.