title: Critical illness polyneuropathy and myopathy (CIPNM): evidence for local immune activation by cytokine-expression in the muscle tissue.
abstract: 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 TNFalphaR75 were also produced locally (IL-1beta in 71%, IFN-gamma in 40%, IL-12 in 73%, TNFalphaR75 in 90%). The anti-inflammatory cytokine IL-10 was simultaneously expressed in 96% of the biopsies. HLA-DR, TNFalphaR75 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.
authors.affiliation: Department of Neurology, St. Elisabeth Hospital Tilburg, Tilburg, The Netherlands. megens-deletter@wxs.nl
authors.forename: M A
authors.initials: MA
authors.lastname: De Letter
authors.forename: P A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: H F
authors.initials: HF
authors.lastname: Savelkoul
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: P I
authors.initials: PI
authors.lastname: Schmitz
authors.forename: A A
authors.initials: AA
authors.lastname: Op de Coul
authors.forename: L H
authors.initials: LH
authors.lastname: Visser
authors.forename: J M
authors.initials: JM
authors.lastname: Kros
authors.forename: J L
authors.initials: JL
authors.lastname: Teepen
authors.forename: F G
authors.initials: FG
authors.lastname: van der Meché
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D016638:Critical Illness; D016207:Cytokines / Q000502:physiology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007150:Immunohistochemistry; D015994:Incidence; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008137:Longitudinal Studies; D009132:Muscles / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009426:Netherlands; D011115:Polyneuropathies / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10