ADRENERGIC REGULATION OF MACROPHAGE-DERIVED TUMOR-NECROSIS-FACTOR-ALPHA GENERATION DURING A CHRONIC POLYARTHRITIS PAIN MODEL

hIncreases in the levels of proinflammatory cytokines, such as TNF alp ha, have been intricately linked with arthritis and the pathogenesis o f several models of neuropathic pain, In addition, arthritis (as well as other types of persistent pain) is associated with increased sympat hetic activity and alterations of other responses in autonomic nervous activity. Adrenergic regulation of LPS-stimulated TNF production by M phi isolated from rats with streptococcal-cell-wall (SCW)-induced art hritis has been examined. Serum TNF levels and the cellular compositio n of peritoneal exudates have also been assessed. M-phi were obtained From: (1) normal control rats, (2) animals injected with complete Freu nd's adjuvant (CFA), (3) rats injected with SCW and arthritic, and (4) those injected with SCW. which failed to develop arthritis. Serum lev els of TNF alpha in rats that develop arthritis are significantly grea ter (2.4 fold) than levels from the other groups. The proportion of OX 19-positive T cell subpopulations are the same in peritoneal exudates from all groups. Immunocytochemical staining also reveals differences between M phi subgroups in the degree of activation. Peritoneal exudat es from rats that develop arthritis contain a greater proportion of th e high TNF producing subclass of M phi, as identified by positive ED3 staining (p < 0.001). In contrast, Ia antigen presenting M phi (OX6-po sitive) in the peritoneal exudate cells are only elevated in rats admi nistered CFA. The selective blockade of adrenergic receptors by idazox an or propranolol demonstrates that the constitutive involvement of ei ther alpha(2) or beta-adrenergic regulation of M phi-derived TNF produ ction is pronounced in rats with arthritis (p < 0.001). These investig ations demonstrate a distinctive pattern of peripheral M phi populatio ns in rats that develop chronic polyarthritic pain. We believe that id entification of interactions between the adrenergic responses and proi nflammatory cytokines will lead to the development of improved strateg ies to treat patients with chronic pain. (C) 1998 Elsevier Science B.V .