Substance P (subP) and Minocycline Suppress Induction of Human Ragweed Specific Memory IgE Responses By Different Mechanisms

Abstract

RationaleWe reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses.MethodsPBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA).ResultsCD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses.ConclusionsSubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses. RationaleWe reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses. We reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses. MethodsPBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA). PBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA). ResultsCD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses. CD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses. ConclusionsSubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses. SubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses.