Critical illness polyneuromyopathy (CIPNM): evidence for local immune activation by cytokine-expression in the muscle tissue

In a longitudinal prospective study a muscle biopsy was taken from 30/32 (33 percent) of the 98 patients who developed critical illness polyneuropathy and myopathy (CIPNM). Neuropathic changes were found in 37 percent, myopathic in 40 percent, and a combination in 23 percent of the biopsies. The immunohistopathology showed macrophages and Th-cells in 40 percent and 60 percent 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 percent, 53 percent and 79 percent respectively. In all biopsies there was an upregulation of both HLA-I and HLA-DR. Proinflammatory cytokines and TNFR75 were also produced locally (IL-1 in 71 percent, IFN- in 40 percent, IL-12 in 73 percent, TNFR75 in 90 percent). The anti-inflammatory cytokine IL-10 was simultaneously expressed in 96 percent of the biopsies. HLA-DR, TNFR75 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.