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The effect of T4 treatment (40 \ g=m\ g, 5 times/ week) on immune function in C57B1/6J mice was studied. The primary antibody synthesis as measured by the plaque-forming cell (PFC) assay demonstrated significant suppression in mice treated with T4 for 30 days. Mitogen assays using PHA and Con A demonstrated significant suppression of cellular immune responses as measured by [3H]thymidine incorporation. The effect was reversed when the treatment was discontinued and a normal response reappeared after 14 days. Allogeneic skin grafts (donor A/J mice) showed prolonged survival (median survival time, 13.5 days) in T4-treated mice as compared to control untreated mice (median survival time, 11 days). Further experiments using Chromium 51 assay for delayed type hypersensitivity also showed suppressed response. These results suggest that treatment with T4, in the above doses and duration, cause immunosuppression in C57B1/6J mice.The ability of various hormones to alter the im¬ mune responses in different animal systems has been well recognized. Of these the immunosuppressive effect of corticosteroids has been well documented (Claman 1975). The direct action of somatotrophic hormones on the immune response has also been shown (Comsa et al. 1974;Fabris et al. 1971). However, studies on the influence of thyroxine on immune responses have been scanty. Fabris (1973) showed that rats thyroidectomized in young adult age exhibited impaired antibody res¬ ponses 45-60 days after operation. Aoki et al. (1976) suggested that thyroxine may cause tumour resistance by increasing the T-cell count and enhancing immunological functions of the host. More recently a stimulating effect of triiodothyronine on cell mediated immunity in humans has been re¬ ported by Balazas et al. (1980). Our studies in C57B1/6J mice showed enhancement of tumour fibrosarcoma T-241 by exogenous thyroxine treat¬ ment (Kumar et al. 1979). Here we present studies done to evaluate the effect of thyroxine on immune responses of C57B1/6J mice. Materials and MethodsMice Female C57B1/6J mice and A/Jax mice (8 to 10 weeks old) were obtained from Jackson Laboratories, Bar Harbor, Maine. T4Purchased from Sigma Chemical Company (St. Louis, Mo.). 131I was obtained from Amersham: Searle Corpo¬ ration, Arlington Hts., Illinois.Treatment with T4 Each mouse injected with 40 µg of T4 (sc) 5 times per week for different durations (7-30 days). Serum T4 and triiodothyronine (T3) levels on treatment were measured by radioimmunoassay. The mean serum T4 and T3 levels in 8 normal controls were 3 ± 0.8 µg% and 132 ± 24 ng%, respectively. During T4 treatment, the levels for T4 and T3 averaged 32.4 ± 5.5 µg% and 523 ± 185 ng%, respectively. There were no noticeable differences in the general condition of mice while on T4 treatment. The average body weights before treatment were 18 ± 1 g and after 30 days of treatment were 18 ± 2 g. treatmentMice were made hypothyroid by treatment with 131I as previously reported (Kumar et al. 1979). Each mouse was on an iodine-free diet before 131I treat...

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57Bl/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10,000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor alpha (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57Bl/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10,000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor alpha (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

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