An innate immune regulatory factor (IIRF) prevents tumorogenesis in a murine melanoma challenge model

Abstract

Biological response modifiers (BRMs) are a family of compounds defined as agents or approaches that modify the host response to pathogens. A serum-derived small peptide, termed Innate Immune Regulatory Factor (IIRF), stimulates the immune response through a natural killer cell-dependent pathway in mice. Ten days after administering a lethal dose of Salmonella typhimurium, 85% of control mice died. No difference was observed between control and mice depleted of natural killer cells and administered IIRF. However, only 30% of natural killer cell intact mice treated with IIRF died by day 10, indicating the critical role of natural killer cells in an IIRF-induced immune response. The protective effects of IIRF were also examined in a natural killer cell-dependent melanoma model. Female B6C3F1 mice were injected with 8 Â 10 5 B16F10 melanoma cells/mouse. Lung samples obtained from control and IIRF treated mice (5 mg on day À1) were analyzed using computerized imaging. Tumor morphometric analysis showed that 53710% of the lung surface from control mice was cancerous. Prophylactic administration of IIRF lowered this value to 3079%, a statistically significant decrease (P ¼ 0.014). When this experiment was repeated with 1 Â 10 5 cells, the number of melanoma nodules on the lung surface could be established through microscopic examination. Control mice (n ¼ 10) had an average of 8877 tumor nodules, whereas IIRF-treated mice (n ¼ 8) had 44712 tumor nodules, a twofold reduction (P ¼ 0.0036). These results suggest that IIRF is a BRM with therapeutic potential for cancer treatment. Drug Dev Res 64: 213-219, 2005.

NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs

“…Thacker and colleagues (34) reported the isolation, structure elucidation, and synthesis of an NME, 1-peptidyl-2-arachidonoyl-3-stearoyl-sn-glyderide, derived from a caprine serum fraction similar to that which had been previously reported (2,20,29,30). The chemical structure is shown in Fig.…”