title: Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2) which accelerates wound healing in mice--a phase I trial in 12 patients.
abstract: Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various growth factors. A novel approach, distinct from the application of single growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several growth factors required for wound healing, which are sequentially released during this process. MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of MALP-2 when applied into small cutaneous wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52-87 years) with different diagnoses were enrolled into the study. An artificial wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 microl MALP-2 (0.125-1 microg) or vehicle control, respectively, was injected intracutaneously into the wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that MALP-2 caused a transient erythema and was tolerated without any systemic side effects up to a dose of 1 microg per wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced local inflammation that faded after 48 h. The effectiveness of MALP-2 in the healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, could now be addressed in further studies.
authors: Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany. niebuhr.margarete@mh-hannover.de
authors: Margarete
authors: M
authors: Niebuhr
authors: Peter F
authors: PF
authors: Mühlradt
authors: Miriam
authors: M
authors: Wittmann
authors: Alexander
authors: A
authors: Kapp
authors: Thomas
authors: T
authors: Werfel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D055666:Lipopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D024141:Collagen Type IV; D055666:Lipopeptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C111835:CCL2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C106335:macrophage stimulatory lipopeptide 2