No signs of immunoactivation in the cerebrospinal fluid during treatment with infliximab.
Neuroinflammatory (demyelinating) disease is a rare but feared complication of treatment with anti-tumour necrosis factor (TNF)alpha in patients with polyarthritis. In this study, blood and cerebrospinal fluid markers of inflammation were analysed in 10 people with polyarthritis before and during treatment with infliximab. An increased systemic expression of interferon (IFN)gamma was detected. Systemic administration of IFNgamma is known to exacerbate multiple sclerosis. However, the present study failed to detect signs of inflammation in the cerebrospinal fluid samples-that is, pleocytosis, oligoclonal immunoglobulin G bands, increased expression of IFNgamma, TNFalpha or interleukin 10, or increased levels of nitric oxide oxidation products. Our initial hypothesis, that the few cases of clinical neuroinflammatory disorders observed during treatment of polyarthritis with anti-TNFalpha represent the extreme end of a commonly occurring minor intrathecal immune activation, which in most cases does not give any overt neurological dysfunction, was not supported. Induction of systemic IFNgamma production may still be relevant in neuroinflammation associated with treatment with anti-TNFalpha.
Andersson
M
M
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. magnus.la.andersson@karolinska.se
Svenungsson
E
E
Khademi
M
M
Lampa
J
J
Brundin
L
L
Wallström
E
E
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001168:Arthritis / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid*; D000069285:Infliximab; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood / Q000134:cerebrospinal fluid; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D002097:C-Reactive Protein; D000069285:Infliximab