Prolactin and prolactin-like polypeptides in rheumatoid arthritis.

A bidirectional communication network exists between the neuroendocrine and immune systems, and a dysfunctional communication may contribute to the development of autoimmune diseases in various species, including humans. Experimental, epidemiological, and clinical data suggest that breast feeding and hyperprolactinemia constitute a risk factor for the development of diseases with autoimmune components, including rheumatoid arthritis (RA). We hypothesized that the anterior pituitary hormone prolactin (Prl) and locally produced Prl-like polypeptides may act as endocrine, autocrine, and paracrine regulators of synovial cell functions. They may participate not only in enhancing T-lymphocyte immune reactivity, but also in the exacerbation of RA lesions through their influence on synovial fibroblasts. In RA synovial tissue, Prl-like polypeptides could participate in a bidirectional communication between immunocytes and fibroblasts. Both Prl and Prl-like polypeptides might act via proto-oncogenes and transcriptional factors, leading to cell proliferation, i.e., synovial tissue hyperplasia, neo-angiogenesis, and the production of catabolic enzymes such as matrix metalloproteinases and cathepsins. In such cases, they could represent important regulators of the T-cell independent mechanism of joint destruction.