Sensitive skin is a condition that exhibits a reduced tolerance to frequent or prolonged use of cosmetics and toiletries. A modern concept of an interactive network between neuropeptides release from cutaneous nerves and immune system has been established in this condition, and its manifestation seems to occur due to increased permeability of the stratum corneum. In response to noxious stimuli, substance P and calcitonin gene-related peptide lead to vasodilation and mast cell degranulation resulting in a process called neurogenic inflammation. Beside neuroendocrine processes, the classical pathways of inflammation are also activated as a consequence of the release of cytokines, histamine and eicosanoids. These, in turn, increase the sensitivity of nociceptors such as TRPV1 (vanilloid receptor channel of transient V1), inducing hyperalgesia and further production of inflammatory mediators. In this study, we evaluated the effects of an active ingredient on the production of neuropeptide substance P (SP); eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4); histamine, TRPV1, and envelope proteins filaggrin and involucrin, using an in vitro model of human keratinocytes. Incubation of keratinocytes cultures with IL-1? promoted significant increases in the levels of SP, PGE2, LTB4, histamine and TRPV1. Concomitant treatment of cell cultures with active ingredient prevented the increase of all evaluated inflammatory mediators. In relation to SP, active ingredient was able to reduce the levels up to 5.6-fold compared to IL-1?-stressed group. The active ingredient also reduced the synthesis of PGE2, LTB4 and histamine and decrease up to 21.5% in the synthesis of TRPV1. Regarding the synthesis of envelope proteins, active ingredient promoted increases up to 3.4- and 2.3-fold, respectively, for filaggrin and involucrin, when compared to control group. The physiopathology of sensitive skin consists of an inflammatory process resulting from the abnormal penetration in the skin of potentially irritating substances because of skin barrier dysfunction and changes in the production of local neuromediators. In this work, it was demonstrated that active ingredient exerts a protective effect against inflammatory reaction induced by IL-1? in human keratinocytes cultures. The results also showed the ability of active ingredient in the stimulation of proteins involved in stratum corneum integrity. Taken together, these data suggest that active ingredient might be considered as an effective additive to skin care products formulations, contributing to the amelioration of the subjective neurosensory forms of discomfort.