Masayoshi Sawaki

Enhanced Interleukin Production after Long-Term Administration of Erythromycin Stearate

The effects of erythromycin stearate (10 mg/kg/day) were studied on productions of interleukin (IL)-1 and -2 in mice after a long-term treatment. A 28-day treatment resulted in higher levels of IL-1 production by macrophages and of IL-2 production by splenocytes, while a 7-day treatment did not increase them. T-cell growth factor activity of IL-2 preparation prepared on day 28 of treatment as determined by HT-2 cell proliferation was reduced by about 40% in the presence of anti-murine IL-4 monoclonal antibodies, while control IL-2 activity was not reduced. Furthermore, a 28-day treatment with erythromycin stearate increased concanavalin A-induced blastogenesis of splenocytes significantly. These results suggest that long-term treatment with erythromycin stearate can stimulate host defense by increasing interleukin production.

Virulence of transparent and opaque colony types of Neisseria gonorrhoeae for the genital tract of mice

The virulence of transparent (Tr) and opaque (Op) colony types of Neisseria gonorrhoeae in the genital tract of female mice was evaluated at two stages of oestrous. Isogenic pairs of Tr and Op variants were isolated from N. gonorrhoeae strain 57-120. Both variants exhibited a T2 morphology, but only the Op variant possessed protein II (P.II) in outer-membrane fractions. When administered by intravaginal inoculation Op gonococci were highly infective only for mice in late pro-oestrous, whereas Tr gonococci were virulent for mice at both late pro-oestrous and dioestrous. Gonococci recovered from the uterus were of both Tr and Op phenotypes in equal proportions when mice were infected at dioestrous with Tr cells. In contrast, greater than 90% of recovered colonies were of Op phenotype when mice were infected at late pro-oestrous with either Op or Tr cells. These results indicate that the virulence of gonococci for the genital tract of female mice differs from that for the chicken embryo. Furthermore, gonococcal survival in the female genital tract might be attributable to phase variation from Tr to Op phenotypes.

Murine tumorlytic factor, immunologically distinct from tumor necrosis factor-α and -β, induced in the serum of mice treated with a T-cell mitogen of Corynebacterium kutscheri

Abstract Murine tumorlytic factor (TF), immunologically distinct from murine tumor necrosis factor (TNF)-α and -β, was purified to a homogeneity from the serum of mice injected with a T-cell mitogen of Corynebacterium kutscheri . The treated mouse serum was purified by Lentil lectin-Sepharose chromatography, DEAE-cellulose chromatography, preparative isoelectric focusing, and high-pressure liquid chromatography to the specific activity of 1.5 × 10 6 U/mg protein. TF was 42 kDa in its oligomeric form and 14 kDa in its monomeric form. TF activity was not impaired with hamster monoclonal antibody (mAb) to recombinant murine TNF-α and -β and, reciprocally, rabbit antibody to TF neutralized the bioactivity of neither murine TNF-α nor -β. TF was not precipitated with the mAb to murine TNF-α and -β in Western blot analysis. The partial amino acid sequence of TF was at most 33% homologous to the 46–63 sequence of mouse TNF-β. Thus, these results suggest that TF might be a novel tumorlytic factor which is immunologically distinct from mouse TNF-α and -β.

Restoration of the acute phase response after infection in cyclophosphamide-treated mice by granulocyte colony-stimulating factor

The therapeutic effect of granulocyte colony-stimulating factor (G-CSF) against intramuscular infection withPseudomonas aeruginosa in cyclophosphamide (CY)-treated mice was analyzed by measuring plasma levels of amyloid P-component (APC) and proinflammatory cytokine levels. CY (100mg/kg) treatment of mice significantly suppressed plasma concentrations of APC and tumor-necrosis factor-α (TNF-α) following infection withP. aeruginosa, in associated with enhanced susceptibility of the treated mice to this bacterium. A 4-day treatment of CY-treated mice with recombinant human G-CSF (rhG-CSF) increased resistance of CY-treated mice, together with the marked restoration of APC and TNF-α productions. The capacity to produce interleukin 1-Β and TNF-α of peritoneal macrophages and also that to produce IL-6 of spleen cells were significantly enhanced by thein vivo administration of rhG-CSF in CY-treated mice. These results indicate that G-CSF may increase the functions of monocytes/macrophages directly or indirectlyin vivo. Therefore, the therapeutic effect of rhG-CSF seems to consist of not only increases in the number and functions of neutrophills but also enhancement of monocyte/macrophage functions.