Profiles of expression of the therapeutic efficacy of KRM-1648 in mice infected with Mycobacterium avium complex at different challenge doses.

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  • マウス実験的Ｍｙｃｏｂａｃｔｅｒｉｕｍ　ａｖｉｕｍ　ｃｏｍｐｌｅｘ感染症に対するＫＲＭ‐１６４８のｉｎ　ｖｉｖｏ治療効果ならびにサイトカイン遺伝子発現に及ぼす接種菌量の影響
  • マウス ジッケンテキ Mycobacterium avium complex カンセンショウ ニ タイスル KRM-1648 ノ in vivo チリョウ コウカ ナラビニ サイトカイン イデンシ ハツゲン ニ オヨボス セッシュキンリョウ ノ エイキョウ

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Abstract

Studied were made on the profiles of the therapeutic efficacy of KRM-1648 (KRM) against Mycobacterium avium complex (MAC) infection, which was induced in mice at different challenge doses, in reducing bacterial growth in the visceral organs and altering the profiles of cytokine m RNA expression at the sites of infection. First, bacterial growth in the lungs of mice infected with either high or low challenge doses of MAC, was reduced due to KRM treatment. This effect was noted even in the early phase of infection (week 4) in mice, that were given a high-dose infection. Second, marked thera peutic efficacy of KRM was observed in mice, that were given low-dose MAC infection, in terms of the reduction in bacterial loads in the spleen. However, in mice given a high-dose bacterial challenge, KRM did not exhibit such an efficacy. Third, the expression of both proinflammatory cytokines (TNF-α, IFN-γ) and anti-inflammatory cytokines (IL-10, TGF-β) in m RNA levels were increased at 4 weeks after infection. Notably, all of the cytokines tested for the m RNA expression levels were higher in mice given a low-dose MAC infection as compared to those in mice given a high-dose infection. KRM treatment increased the m RNA levels of these cytokines at week 4, while TGF-β m RNA expression at week 8 was conversely decreased by KRM treatment. These findings suggest that the profiles of the therapeutic efficacy of KRM vary in mice given low-or high-dose MAC infection.

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