The Role of Cathelicidin LL-37 in the Pathogenesis of Microbial Eczema: Mechanisms of Immune Dysregulation and Therapy Perspectives

Microbial (nummular) eczema is a common chronic inflammatory skin disease, the pathogenesis of which is closely linked to impaired innate immunity and colonization by Staphylococcus aureus. Despite significant advances in the understanding of dermatoses, the role of specific effector molecules, particularly cathelicidin LL-37, in the transition from an acute to a chronic process remains insufficiently studied, and existing therapeutic approaches do not always achieve sustained remission. Aim of the review: to conduct a comprehensive analysis of the molecular and cellular mechanisms of involvement of the antimicrobial peptide cathelicidin LL-37 in the development and chronicity of microbial eczema, and to evaluate potential therapeutic strategies aimed at modulating its activity. Materials and methods: the review presents a systematic analysis of data from the scientific literature for the period 2010–2025, selected from the databases PubMed, Scopus, Web of Science, CyberLeninka, and eLibrary. Combinations of key words were used: “cathelicidin LL-37”, “hCAP-18”, “antimicrobial peptides”, “microbial eczema”, “nummular dermatitis”, “Staphylococcus aureus”, “eczema pathogenesis”, “skin innate immunity”. Results. It has been established that cathelicidin LL-37 functions as a key molecular hub integrating epidermal barrier dysfunction, bacterial colonization, and chronic immune inflammation in microbial eczema. Its role is characterized by profound duality. On the one hand, the intact peptide has direct bactericidal activity against S. aureus, promotes wound healing, and supports skin homeostasis. On the other hand, under the conditions of microbial eczema, its pathological transformation occurs: proteolytic cleavage by bacterial and intrinsic skin proteases leads to the generation of pro-inflammatory fragments (KS-30, RK-31), which, through the activation of Toll-like receptors (TLR2/4) and the purinergic receptor P2X7, induce the production of interleukin-1β, interleukin-6, interferon-gamma, and potent neutrophil chemotaxis. This creates a self-sustaining vicious cycle of inflammation. An additional pathogenetic factor is an imbalance in the antimicrobial peptide system, in particular, a relative deficiency of dermcidin and β-defensins. Conclusion. The pathogenesis of microbial eczema significantly depends on the dysregulation of cathelicidin LL-37, which transforms from a protective factor into a trigger of chronic inflammation. This shifts the treatment paradigm from empirical antibiotic therapy and corticosteroids to targeted approaches. The most promising strategies appear to be those aimed at inhibiting specific staphylococcal proteases, blocking pro-inflammatory receptors (TLR, P2X7), using stable LL-37 analogs, and correcting the overall balance of antimicrobial peptides. The development and implementation of such methods could improve the efficacy of managing resistant and recurrent forms of the disease.

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