Журнал цитокиновой биологии

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Topical Application of 2% Lithium Carbonate Reduces Pain, Swelling and the Chemokine KC-GRO (Murine IL-8) in a MSU-induced Model of Gout in Rat Ankle

Carl Ganio

Background: The level of Mono Sodium Urate (MSU) in the human should be ideally kept below 6.o mg/dl. Above 6.8-7.2 mg/dl, crystallization may occur in tissues; resulting in the inflammatory response understood as acute gout attack. Alfred Baring Garrod and Alexander Ure felt that these concretions in the synovial tissues and kidneys of chronic gout could be dissolved. Garrod’s 1859 text “The Nature and Treatment of Gout and Rheumatic Gout” should be considered one of the most complete texts discussing the topic from antiquity, through the mid-19th century. The application of lithium carbonate directly to gouty tophi was one treatment Garrod advocated. He felt that the MSU concretion could be dissolved if the more-soluble lithium urate moiety was formed. Garrod demonstrated the solvent effects of lithium by dissolving the gouty tophus in a metacarpal bone dropped into solution. Thomas Edison in 1890 presented “An Account of Some Experiments of Electrical Endosmose to the Treatment of Gouty Concretion”. It became evident the dilute solutions of the lithium salts are not solvents for uric acid or urates and results such as Garrod’s metacarpal experiment worked only when in concentrated solution. Edison’s own lab showed that there were better solvents for urates; and by 1893 lost interest in the use of lithium for dissolution of gouty concretions. The use of Lithium for the treatment of gout persists today only as a historical reference; due in part to the often-cited Abramowitsch text “Treatment by Ion Transfer (Iontophoresis)”. This study was undertaken in an attempt to validate the beneficial effects of topical lithium on gout; as seen by the author in his anecdotal off-label use of 2% lithium carbonate in 25 patients. Methods: A proof-of-concept study was personally-commissioned by the author. Topical application of a 2% lithium carbonate solution was tested in an MSU Acute Gout Model induced via injection into the ankles of rats. Clinical observation of swelling and pain index was determined. Cytokines and chemokines were measured in the synovial fluid. Histopathology was performed after necropsy on the banked ankles. Results: The observed pain index and swelling due to MSU-induced gout attack was slightly decreased by the topical application of 2% lithium carbonate/10% DMSO solution to male Sprague Dawley rat ankles. Cytokines IL-1b, IL-6, and TNF-a were increased. Unexpected reduction in the chemokine KC-GRO (murine IL-8) was seen. The histopathology showed anticipated findings in the MSU control; edema, synovial hyperplasia, and large rafts of inflammatory cells/WBCs within the synovium of the rat ankle. DMSO vehicle alone reduced appearance of inflammation. The addition of 2% Lithium Carbonate produced a more significant reduction in the thickening of the synoviocytes and the appearance of inflammatory cells within the synovial fluid was also more markedly reduced by the addition of Lithium. Conclusion: Topical application of 2% lithium carbonate compounded with 10% DMSO reduces the pain, swelling and inflammation of a MSU-induced gout attack in the ankle of male Sprague Dawley rats. The reduction of the chemokine KC-GRO suggests that analogous reduction of IL-8 in the human may explain the beneficial effects seen in the author’s anecdotal success using topical 2% lithium carbonate in 25 patients.