LPS-induced knee-joint reactive arthritis and spinal cord glial activation were reduced after intrathecal thalidomide injection in rats.
OBJECTIVE
Thalidomide is thought to prevent TNF-α production, and such mechanism could be useful in a spinally delivered drug approach for the control of peripheral inflammation. This study aimed to evaluate the effect of intrathecal thalidomide, in comparison with that of intraperitoneal treatment, on articular incapacitation, edema, synovial leukocyte content, and spinal cord glial activation in a model of Escherichia coli lipopolysaccharide (LPS)-induced reactive arthritis in rats.


METHODS
LPS (30ng) was injected into a knee-joint previously primed with carrageenan (300μg). Systemic (30 and 100mg/kg; intraperitoneal, i.p.) and intrathecal (10 and 100μg; i.t.) thalidomide were given 1h or 20min before LPS injection, respectively. Articular incapacitation and edema were evaluated hourly. After 6h, synovial fluid and lumbar spinal cords were collected for subsequent evaluations of cell migration and expression of CD11b/c and GFAP markers, respectively.


RESULTS
Systemic (30 and 100mg/kg) or intrathecal (10 and 100μg) thalidomide reduced articular incapacitation, edema, and polymorphonuclear migration. In addition, i.p. and i.t. thalidomide reduced the expression of CD11b/c and GFAP markers in the lumbar spinal cord. These results suggest that thalidomide can also produce peripheral anti-inflammatory effects through action in the spinal cord that may involve glia inhibition.


CONCLUSIONS
This study provides new evidence that the direct spinal delivery of immunomodulators may be an alternative for the treatment of arthritic diseases, which require long systemic treatment with drugs associated with undesirable side effects.
Bressan
Elisângela
E
Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Trindade, Florianópolis, Santa Catarina, 88040-900, Brazil.
Mitkovski
Mišo
M
Tonussi
Carlos Rogério
CR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007719:Knee Joint / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide