Nevertheless, Pa-MAP seems to be unable to

interact with immune system cells to induce cytokine production. Data presented here shows that Pa-MAP neither significantly stimulates nor inhibits some cytokine production, despite of others could be modified by the presence of peptide. This result is similar to the Fritsche et al. studies [17]. In their studies, it was demonstrated that a short, proline-rich antimicrobial peptide has direct antibacterial action in vivo, but was unable to stimulate cytokine production. Despite this website the absence of immunomodulatory activity, data reported here shows strong evidence that the peptide Pa-MAP could be useful for pharmaceutical design once it shows the ability to perform E. coli inhibition in vivo. Pa-MAP demonstrated in vivo activity against E. coli at low concentrations when compared to other antimicrobial peptides. Schaal et al. [51] demonstrated similar effect with rhesus θ-defensin (RTD), a macrocyclic antimicrobial peptide expressed in leukocytes of Old World monkeys. This RTD peptide was administrated at a single subcutaneous dose at 5 mg kg−1 in mice previously intraperitoneally infected with E. coli and resulted in an increase in mice survival. Vingsbo et al. [60] demonstrated

that the CHIR-99021 concentration novel synthetic polymyxin derivatives NAB737 and NAB739 are as effective as polymyxin B, an effective antibiotic against Gram-negative bacterial infections, in effectively treating E. coli peritoneal infection in mice at 1, 2 and 4 mg kg−1. In another study, a non-natural AMP named M33 (with 9 amino acid residues long) showed the ability at 12.5 and 25.0 mg kg−1 to protect 100% of mice infected with lethal

doses of E. coli and P. aeruginosa. Lower concentrations were unable to protect mice [42]. Although antimicrobial activity, the mechanism of action has been unclear until now. Some researchers have suggested PJ34 HCl that AMPs can cause bacterial membrane disruption, leading to intracellular leakage and later microorganism death [4]. In addition, AMPs can interact with immune cells and increase immune response in the face of injury or inflammation, modulating the innate immune response, for example, through chemotactic activity, stimulation of cytokine release, neutralization of LPS-induced septic effects, wound healing and tissue repair [11]. Nevertheless, Pa-MAP did not exhibit the ability to stimulate cytokine release from immune cells as previously described, suggesting that direct microorganism control could be related to the Pa-MAP mechanism of action. One of the most documented effects of E. coli infection is progressive weight loss, mainly due to water loss during infection [44].