Studies on the Therapeutic Efficacy of Antibiotics, Immunosuppressants and an Immunomodulator in Mycoplasma pulmonis-Induced Pneumonia of Mice

It is widely known that cell-mediated immunity is activated during mycoplasma infection, and it is considered that cell-mediated immune response might contribute to the formation of lung lesions during mycoplasma infection in man. However, the treatment of mycoplasma pneumonia using antibiotics with immunosuppressants or immunomodulators has not yet been examined in detail. This study was performed as fundamental research to apply immunosuppressants or immunomodulators to mycoplasma pneumonia in man. A mouse model of mycoplasma pneumonia was first established using Mycoplasma pulmonis. Mice were treated with either minocycline (MINO), the immunosuppressants, prednisolone (PSL) or cyclosporin A (CYA), or the immunomodulator, interleukin-2 (IL2), or a combination of MINO, immunosuppressants and immunomodulator. The mice were treated every day from day 3 to day 9 after inoculation. The effects of treatment on lung lesions, the isolation of mycoplasma organisms and host reactions were compared between the experimental groups, and the following results were obtained. 1) Treatment with MINO reduced inflammatory cell infiltration in the alveoli (alveolar lesion), but did not reduce peribronchial nor periarterial cuffing with mononuclear cells, i. e., lymphocytes and plasma cells (interstitial lesion). This treatment could not completely eliminate mycoplasma organisms from the lung. 2) Treatment with MINO and immunosuppressive agents (PSL or CYA) reduced both alveolar lesion and interstitial lesion, but the number of mycoplasma organisms in the lung remained at the same level as in the mice treated with MINO alone. Both humoral and cellular immune responses were suppressed in the host animals. 3) In mice treated with MINO and IL2, slight interstitial lesion was observed. Alveolar lesion was also reduced and many macrophages were found infiltrated in the alveoli 2 weeks after inoculation. The number of mycoplasma organisms in the trachea and lung were the least among the experimental groups. Both specific antibody response and nonspecific cell-mediated immune response were activated in the host animals. The results of this treatment suggested that the immune responsiveness of the host animal played an important role in eliminating mycoplasma organisms. 4) Interstitial lesion was reduced by treatment with CYA alone, on the other hand increased by IL2 alone. The results suggested that cell-mediated immune response might contribute to the formation of the interstitial lesion. These data suggest that there are two methods of therapy with antibiotics for mycoplasma pneumonia: one is the nonspecific suppression of cell-mediated immune responsiveness in the host, while the other is the nonspecific activation of cell-mediated immune responsiveness in the host