In a longitudinal prospective study a muscle biopsy was taken from 30/32 (33%) of the 98 patients who developed critical illness polyneuropathy and myopathy (CIPNM). Neuropathic changes were found in 37%, myopathic in 40%, and a combination in 23% of the biopsies. The immunohistopathology showed macrophages and Th-cells in 40% and 60% of the muscle biopsies respectively. Small mainly perivascular infiltrates contained macrophages and Th-cells. ICAM-1, VCAM and MAC were found on the vascular endothelium in 58%, 53% and 79% respectively. In all biopsies there was an upregulation of both HLA-I and HLA-DR. Proinflammatory cytokines and TNFαR75 were also produced locally (IL-1β in 71%, IFN-γ in 40%, IL-12 in 73%, TNFαR75 in 90%). The anti- inflammatory cytokine IL-10 was simultaneously expressed in 96% of the biopsies. HLA-DR, TNFαR75 and IL-10 differed significantly when compared with control muscle biopsies. Our data provide evidence that small numbers of activated leukocytes producing both pro- and anti-inflammatory cytokines infiltrate skeletal muscle of CIPNM patients. We propose that the local balance of leukocyte activities is of importance in the pathophysiology of muscle weakness in CIPNM. (C) 2000 Elsevier Science B.V.

Critical illness polyneuropathy and myopathy, Cytokines, Immune activation, Immunohistochemistry, Muscle biopsy, Sepsis,
Journal of Neuroimmunology
Department of Pathology

de Letter, M.A.C.J, van Doorn, P.A, Savelkoul, H.F.J, Laman, J.D, Schmitz, P.I.M, Op de Coul, A.A.W, … van der Meché, F.G.A. (2000). Critical illness polyneuropathy and myopathy (CIPNM): Evidence for local immune activation by cytokine-expression in the muscle tissue. Journal of Neuroimmunology, 106(1-2), 206–213. doi:10.1016/S0165-5728(99)00252-0