Evidence that scabies mites (Acari: Sarcoptidae) influence production of interleukin-10 and the function of T-regulatory cells (Tr1) in humans.

We performed experiments to determine whether an extract of Sarcoptes scabiei (De Geer) influenced cytokine expression by human T-lymphocytes. Peripheral blood mononuclear cells from five sensitized donors and four donors without sensitization to scabies mites were challenged with a T-cell mitogen alone, with scabies extract (SS) alone, or with mitogen and SS together. Supernatants were analyzed for the cytokines interferon-gamma (IFNgamma), interleukin (IL)-2, IL-4, and IL-10. No IL-2 or IL-4 was produced in response to scabies extract. Cells from both naive and sensitized donors produced large amounts of IFNgamma and IL-10. The lack of IL-4 but high levels of IL-10 suggests that IL-10 was likely secreted by type 1 T-regulatory cells, which were activated by something in the scabies extract. IL-10 has anti-inflammatory and immune-suppressive effects. It may play a key role in depressing the inflammatory and immune responses in humans so that clinical symptoms are not seen until 4-6 wk after a person becomes infested with scabies mites.

Granulocyte-macrophage colony-stimulating factor is a chemoattractant cytokine for human neutrophils: involvement of the ribosomal p70 S6 kinase signaling pathway.

GM-CSF stimulates proliferation of myeloid precursors in bone marrow and primes mature leukocytes for enhanced functionality. We demonstrate that GM-CSF is a powerful chemotactic and chemokinetic agent for human neutrophils. GM-CSF-induced chemotaxis is time dependent and is specifically neutralized with Abs directed to either the ligand itself or its receptor. Maximal chemotactic response was achieved at approximately 7 nM GM-CSF, and the EC(50) was approximately 0.9 nM. Both concentrations are similar to the effective concentrations of IL-8 and less than the effective concentrations of other neutrophil chemoattractants such as neutrophil-activating peptide-78, granulocyte chemotactic protein-2, leukotriene B(4), and FMLP. GM-CSF also acts as a chemoattractant for native cells bearing the GM-CSF receptor, such as monocytes, as well as for GM-CSF receptor-bearing myeloid cell lines, HL60 (promyelomonocyte leukemic cell line) and MPD (myeloproliferative disorder cell line), following differentiation induction. GM-CSF induced a rapid, transient increase in F-actin polymerization and the formation of focal contact rings in neutrophils, which are prerequisites for cell migration. The mechanism of GM-CSF-induced chemotaxis appears to involve the cell signaling molecule, ribosomal p70 S6 kinase (p70S6K). Both p70S6K enzymatic activity and T(421)/S(424) and T(389) phosphorylation are markedly increased with GM-CSF. In addition, the p70S6K inhibitor hamartin transduced into cells as active protein, interfered with GM-CSF-dependent migration, and attenuated p70S6K phosphorylation. These data indicate that GM-CSF exhibits chemotactic functionality and suggest new avenues for the investigation of the molecular basis of chemotaxis as it relates to inflammation and tissue injury.