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Inhibitory Effects of Glucosamine on Endotoxin-Induced Uveitis in Lewis Rats

¹From the Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China; the ²Department of Ophthalmology, Kaohsiung Armed Force General Hospital, Kaohsiung, Taiwan, Republic of China; the ³Department of Pharmacy, Tajen University, Pintung, Taiwan, Republic of China; and the ⁴Department of Ophthalmology, National Defense Medical Center, Taipei, Taiwan, Republic of China.

PURPOSE. Glucosamine sulfate (GS) is a naturally occurring sugar that exerts immunosuppressive effects in vitro and in vivo. The authors investigated whether GS modulates the inflammatory reaction in endotoxin-induced uveitis (EIU) of rats and the mechanisms by which it exerts its effects.

METHODS. Two-hundred micrograms of lipopolysaccharide (LPS) was injected subcutaneously into Lewis rats to induce EIU. Doses of GS (10, 100, or 1000 mg/kg) were divided into three aliquots and administered intraperitoneally 30 minutes before LPS injection, concurrently with LPS injection, and 30 minutes after LPS injection. Twenty-four hours after LPS injection, aqueous humor was collected for cell counting and measurement of protein concentration. Immunohistochemical staining of the iris-ciliary body was performed to evaluate the effects of GS on intercellular adhesion molecule (ICAM)-1 and nuclear factor (NF)-B activation and to demonstrate macrophage infiltration. The effects of various doses of GS pretreatment were also examined using a mouse macrophage cell line (RAW264.7 cells) and LPS stimulation. Levels of prostaglandin (PG)-E2 and nitric oxide (NO) were determined. Expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured using Western blot analysis. The effect of GS on LPS-induced NF-B activation in RAW cells was also examined.

RESULTS. Cell counting and analysis of protein concentration in aqueous humor revealed that GS suppressed EIU in rats treated with a high dose of GS (1000 mg/kg). Immunohistochemistry showed that treatment with GS reduced ICAM-1 expression and suppressed activation of NF-B in the iris-ciliary body. The main inflammatory cells in the iris-ciliary body during EIU were macrophages. In LPS-stimulated macrophage RAW cell culture, GS inhibited the production of NO and PG-E2, the expression of iNOS and COX-2, and the activation of NF-B.

CONCLUSIONS. GS suppresses EIU in rats by blockading the NF-B–dependent signaling pathway and the subsequent production of ICAM-1 and proinflammatory mediators. This study has extended the authors’ previous observation that GS is a potentially important compound for reducing ICAM-1–mediated inflammatory effects in the eye.