interleukin-8 and Skin-Diseases--Bacterial

An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity.. To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation.. Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation.. The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 μmol L(-1)). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes.. Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Calcium; Cells, Cultured; Erythema; Gram-Positive Bacterial Infections; Helicobacter pylori; Humans; Injections, Intradermal; Interleukin-8; Keratinocytes; Mice, Inbred ICR; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; NF-kappa B; Peptide Fragments; Propionibacterium acnes; Ribosomal Proteins; RNA, Messenger; Skin Diseases, Bacterial; Toll-Like Receptor 2

The etiology of acne is a complex process, and acne is one of the most common skin disorders affecting millions of people. The pathogenesis of acne is closely associated with the bacterium, Propionibacterium acnes which was previously known as Corynebacterium parvum. Both viable and non-viable P. acnes/C. parvum have been shown to induce an immunostimulatory effect in vivo, suggesting that even dead bacteria continue to activate an inflammatory response. Acne treatments with lasers or devices, induce a bactericidal effect through heat generation which may not address the immunogenic activity of P. acnes and the resulting acne inflammation. Therefore, we sought to determine whether killed P. acnes is capable of inducing an inflammatory response and therefore could be a contributing factor in acne. Direct heat treatment of P. acnes cultures with temperatures ranging from 50 degrees C to 80 degrees C reduced P. acnes viability. Both viable and heat-killed P. acnes activated the p38 MAP kinase and its downstream substrate Hsp27. Stimulating keratinocytes with normal and heat-inactivated P. acnes resulted in an induction of proinflammatory nitric oxide and IL-8 production. Thus killed P. acnes is capable of inducing inflammation in skin suggesting that therapies that have both bactericidal and anti-inflammatory effects may result in a more effective treatment of patients with acne than treatments that are bactericidal alone.

Topics: Acne Vulgaris; Cells, Cultured; Heat-Shock Proteins; Hot Temperature; HSP27 Heat-Shock Proteins; Inflammation; Interleukin-8; Keratinocytes; Microbial Viability; Molecular Chaperones; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Propionibacterium acnes; Skin; Skin Diseases, Bacterial

Tumor necrosis factor (TNF)-alpha exerts both physiologic and pathologic effects in response to infection, conferring the benefit of host defense against infection at the risk of eliciting severe pathology if the response is excessive or inappropriate. In the present study, the effects of an anti-TNF-alpha monoclonal antibody (MAb) and a TNF-alpha receptor construct (p75-Fc) were compared with that of saline in a primate model of subcutaneous abscess induced with Staphylococcus aureus. Intravenous administration of anti-TNF-alpha MAb delayed the onset and reduced the incidence and the severity of abscess formation in response to inoculation with S. aureus at concentrations of 10(9) and 10(10) cfu/mL, compared with administration of saline. In contrast, no improvement in abscess formation was observed in animals treated with p75-Fc. These results supply initial evidence that anti-TNF-alpha MAb, unlike p75-Fc, provides a beneficial effect in this abscess model.

Topics: Abscess; Animals; Antibodies, Monoclonal; Etanercept; Female; Immunoglobulin G; Interleukin-12; Interleukin-8; Macaca mulatta; Male; Receptors, Tumor Necrosis Factor; Skin Diseases, Bacterial; Tumor Necrosis Factor-alpha