Hemoglobin protects from streptococcal cell wall-induced arthritis.
OBJECTIVE
To investigate the ability of hemoglobin (Hgb), a nitric oxide (NO) scavenger, to deplete excess NO and reduce inflammation and injury in synovial tissue from joints with inflammatory arthritis.


METHODS
The severity of streptococcal cell wall-induced arthritis was monitored following administration of Hgb. Plasma nitrite and nitrate levels were measured, and inducible NO synthase (iNOS) and cytokine messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) and joint tissue were evaluated.


RESULTS
Following systemic administration of Hgb to arthritic rats, plasma levels of nitrite and nitrate as well as iNOS mRNA expression in the joints and PBMC were significantly reduced. Moreover, inflammatory cell accumulation and disease pathology in the joint tissue were dramatically attenuated without obvious side effects. Consistent with this reduction in the inflammatory response, cytokine gene expression was decreased in the synovium of Hgb-treated rats.


CONCLUSIONS
Modulation of NO levels through the use of a NO scavenger, Hgb, influences the development and severity of arthritis. These findings suggest that depletion of excess NO by NO scavengers provides a prototype for further exploration of potential treatments for chronic arthritis.
McCartney-Francis
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NL
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4352, USA.
Song
X Y
XY
Mizel
D E
DE
Wahl
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CL
Wahl
S M
SM
D000818:Animals; D001170:Arthritis, Infectious / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005856:Germ-Free Life; D006454:Hemoglobins / Q000494:pharmacology*; D007150:Immunohistochemistry; D007596:Joints / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D006454:Hemoglobins; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat