THE ADHESION MOLECULE AND CYTOKINE PROFILE OF MULTIPLE-SCLEROSIS LESIONS

The expression of the adhesion molecules, vascular cell adhesion molec ule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and the ir respective receptors on leukocytes, very late activation antigen-4 (VLA-4) and lymphocyte function-associated antigen-1 (LFA-1), together with a selection of proinflammatory and immunomodulatory cytokines (i nterleukin [IL]-1, IL-2, IL-4, IL-10, tumor necrosis factor-alpha [TNF -alpha], transforming growth factor-beta [TGF-beta], and interferon-ga mma [IFN-gamma]) was examined by immunocytochemistry in multiple scler osis (MS) lesions of different ages and compared with central nervous system (CNS) tissue from other neurological diseases, both inflammator y and noninflammatory, and normal CNS tissue. These molecules play key roles in lymphocytic infiltration and interactions during tissue infl ammation and are in large part normally not expressed by CNS cells. Hi gh levels of expression of all the molecules tested were found in MS, particularly in chronic active lesions. Positivity for all molecules w as also seen in other neurological diseases, even in noninflammatory c onditions. There was some suggestion that the VCAM-1/VLA-4 adhesion pa thway was expressed at higher levels in chronic MS lesions, while ICAM -1/LFA-1 was used more uniformly in lesions of all ages. Of the cytoki nes examined, there was increased expression of TNF-alpha and IL-4 in MS; this was found to be statistically significant when compared with noninflammatory neurological diseases. The expression of most adhesion molecules and some cytokines was negligible in normal CNS tissue alth ough low-level reactivity for ICAM-1 TGF-beta, IL-4, TNF-alpha, and IL -10 was detected, perhaps indicative of immunoregulatory mechanisms. M icroglial cells and astrocytes were the major CNS cell types expressin g cytokines. The results indicate a potential in the CNS for widesprea d induced expression of molecules involved in the inflammatory cascade . No adhesion or cytokine molecule or pattern of expression unusual fo r MS was apparent.