ラットの結核感染においてレチノイン酸経口投与は
肺内リンパ球、マクロファージ数の増加とサイトカイン発現を誘導し、病態の軽減に有効である

Retinoic Acid Therapy Attenuates the Severity of Tuberculosis While Altering Lymphocyte and Macrophage Numbers and Cytokine Expression in Rats Infected with Mycobacterium tuberculosis.

Hiroyuki Yamada, Satoru Mizuno, A. Catharine Ross, and Isamu Sugawara

Journal of Nutrition, 137: 2696-2700, 2007. に掲載された論文の要旨と図表を掲載したものです。


【目的】ビタミンAの誘導体の一つで生理活性が高いレチノイン酸(RA)は、マクロファージを刺激し、一方、結核菌は肺胞マクロファージを標的として感染することから、ラットの結核感染におけるRAの治療的効果を検討した。

【材料と方法】Wister-Lewisラット15匹を結核菌H37Rvで吸入感染し、体重100gあたり100μgのRAを食物油に溶解して週3日、3-5週間経口投与し、完了後解剖し、肺および脾臓内生菌数、組織内サイトカインmRNAの定量（real-time PCR）、病理組織像の検討を行った。

【結果と結論】RA投与群と対照群（食物油のみ投与）間で肺の組織像の上での病態に差が見られ、感染後３週、5週の肺および脾臓内生菌数はRA投与群で有意に減少していた(p<0.005)。感染肺組織内のCD4+, CD8+T細胞、NK細胞、CD163陽性マクロファージ数は、RA投与群で増加していた。また、RA投与群の感染肺組織におけるIFN-γとiNOS mRNAの発現量は対照群と比較して有意に多かった。更に、RA投与ラットからBALで得た肺胞マクロファージをin vitroで結核菌感染すると、対照群由来の肺胞マクロファージと比較して、IFN-γ, TNF-α, iNOS, IL-1β, IL-10, IP-10 mRNAの発現レベルが高かった。以上の結果から、RAの経口投与が結核菌のin vivo増殖を抑制し、病態の進展を押さえることが示唆された。

figure 1 RA administration(RA+) significantly decreased lung and spleen CFU in M.tuberculosis H37Rv-infected rats.figure 2 Histopathology of M. tuberculosis H37Rv-infected RA-treated rats(A-C) and H37Rv-infected control rats(D-F)table 1 Flow cytonietric analysis of lung BAI.table 2 Cytokine ralative mRNA levels 18-h postinfection in control(RA-) and RA-treated(RA+)rat lung BAL cells infected in vitro with M.tuberculosis H37Rv
【文献】
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updated 07/12/05