Effects of interleukin-2 and cyclosporin A on pathologic features in Mycoplasma pneumonia.

Abstract

To elucidate the immunopathologic mechanisms of Mycoplasma pneumonia, the effects of interleukin-2 (IL-2) and cyclosporin A (CYA) on Mycoplasma pneumonia in mice were investigated. Mice were intranasally inoculated with Mycoplasma pulmonis (M. pul) and treated with IL-2, CYA, or minocycline (MINO) every day between Days 3 and 9. They were killed at Days 7, 14, or 21 after the inoculation. Cell-mediated immunity (CMI) of the host was assessed by delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC). Peribronchial and perivascular lymphocyte cuffing and the accumulation of macrophages at the ends of bronchioles were exacerbated (p < 0.05) in IL-2-treated mice at Day 14 and reduced (p < 0.05) in CYA-treated mice at Day 7. Although the DTH responses to SRBC of saline-inoculated, IL-2-treated mice were increased at Days 7 (p < 0.01) and 14 (p < 0.05), those of M. pul-inoculated, IL-2-treated mice at Day 7 could not recover to the control level. The CMI levels of M. pul-inoculated, CYA-treated mice were decreased at Days 7, 14 (p < 0.05), and 21 (p < 0.01). Mycoplasma organisms in the lung showed the greatest decrease (p < 0.05) in MINO- and IL-2-treated mice, but increased at Day 21 (p < 0.05) in mice treated with IL-2 alone. These results suggest that the pathologic features of Mycoplasma pneumonia could be modified by the degree of host CMI.

Relationships between radiological pattern and cell-mediated immune response in Mycoplasma pneumoniae pneumonia

“…IL-2 treatment enhanced the level of CMI and, simultaneously, exacerbated peribronchial lymphocyte infiltration and accumulation of macrophages at the ends of bronchioles; these pathological lesions were mimicking nodular opacities on CT of human MP. In contrast, CyA treatment depressed CMI, reduced peribronchial lymphocyte infiltration and exacerbated intra-alveolar inflammatory cell accumulation; these pathological changes may correspond to airspace consolidation on CT of human MP [18]. These findings supported the suggestion that the pathological pattern of lung lesions in MP might reflect the level of host CMI.…”

“…These pathological findings mimic those of a mouse mycoplasma model. We previously reported [18] the effect of interleukin-2 (IL-2) as a T-cell activator and cyclosporin A (CyA) as a T-cell selective suppressor on pulmonary lesions in such an animal model of mycoplasma infection. IL-2 treatment enhanced the level of CMI and, simultaneously, exacerbated peribronchial lymphocyte infiltration and accumulation of macrophages at the ends of bronchioles; these pathological lesions were mimicking nodular opacities on CT of human MP.…”

Mycoplasma pneumoniae as an Under- Recognized Agent of Vasculitic Disorders

“…Among a number of cytokines reported to be associated with the pathomechanism of M. pneumoniae pneumonia, the author and coworkers have demonstrated that the macrophage-derived cytokines interleukin-18 and interleukin-8 play significant roles in the development of pneumonia and are directly related to disease severity [Narita et al, 2000[Narita et al, , 2001aTanaka et al, 2002]. Interleukin-18 is an immune regulatory cytokine that functions as an activator of T cells and a subsequent cascade of T helper-1 and T helper-2 type cytokines [Tanaka et al, 1996]. Interleulin-8 is an inflammatory cytokine and functions as an activator of neutrophils.…”

“…As regards the presence of pneumonia in relation to the development of extrapulmonary diseases, the author and coworkers have found, using polymerase chain reaction methodology [Narita et al, 1992], that the genome of M. pneumoniae can be detected more frequently in serum from patients without pneumonia than in serum from patients with pneumonia [Narita et al, 1996]. This means that pneumonia, which is a consequence of the local host immune response occurring on the respiratory surface, plays an important role as a kind of fire-wall preventing dissemination of the organism beyond the respiratory tract [Cartner et al, 1998;Tanaka et al, 1996]. In this regard, it is important to note that directtype extrapulmonary manifestations not infrequently occur in the absence of pneumonia, which is a hallmark of mycoplasmal infecti o n .…”

Significant Role of Interleukin-8 in Pathogenesis of Pulmonary Disease Due to Mycoplasma pneumoniae Infection

“…Researchers have reported that the cell-mediated immune response of the host, specifically through the function of Th1-type cytokines, has a critical role in the development of clinical manifestations and pathologic features of M. pneumoniae infection (11,12). More recently, it was reported that interleukin-18 (IL-18), a regulatory cytokine for Th1-type cytokines, plays an important role in pulmonary disease manifestation due to M. pneumoniae (5).…”