olopatadine-hydrochloride and Dermatitis--Contact

Intense pruritus and cutaneous reactivity represent cardinal features of eczema. The resulting scratching behaviors alter neuronal conditions of the spinal dorsal horn where the primary sensory afferent fibers transmit cutaneous stimulation and deteriorate eczematous skin lesions. We investigated the effects of olopatadine hydrochloride (olopatadine) on alteration of neuronal conditions of the spinal dorsal horn and eczematous skin lesions induced by contact dermatitis. Eczematous lesions were induced by repeated application of diphenylcyclopropenone (DCP) in BALB/c mice. Olopatadine suppressed scratching behavior caused by repeated application of DCP in mice. Increased expressions of c-Fos and substance P in the spinal dorsal horn following DCP application were improved by olopatadine. Furthermore, olopatadine diminished the number of infiltrating cells and levels of cytokines in eczematous skin lesions resulting from DCP application. Olopatadine improves neurological conditions in the spinal cord and eczematous skin lesions in a murine contact dermatitis model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cyclopropanes; Dermatitis, Contact; Dibenzoxepins; Dose-Response Relationship, Drug; Eczema; Female; Histamine H1 Antagonists; Immunohistochemistry; Mice; Mice, Inbred BALB C; Neurons; Olopatadine Hydrochloride; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Pruritus; Skin; Substance P

Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use.. We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity.. Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine.. These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.

Topics: Animals; Chronic Disease; Dermatitis, Contact; Dibenzoxepins; Glucocorticoids; Histamine H1 Antagonists; Interleukin-4; Male; Mice; Mice, Inbred BALB C; Models, Animal; Olopatadine Hydrochloride; Prednisolone; Recurrence; Substance Withdrawal Syndrome

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Topics: Animals; Anti-Inflammatory Agents; Antipruritics; Chlorpheniramine; Cytokines; Dermatitis, Contact; Dibenzoxepins; Dose-Response Relationship, Drug; Ear; Histamine H1 Antagonists; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nerve Growth Factor; Olopatadine Hydrochloride; Oxazolone; Prednisolone; Pruritus; Severity of Illness Index

Olopatadine hydrochloride (olopatadine) is one of the second-generation antihistamines, which is prescribed for allergic disorders such as rhinitis, urticaria and eczema dermatitis.. To investigate the possible anti-inflammatory effect of olopatadine on the chronic contact hypersensitivity response to repeated topical application of oxazolone in mice.. The preventive and therapeutic effects of oral olopatadine were quantified by measurements of ear swelling, cytokine protein and mRNA expression in the ear lesion, and were compared with those of topical betamethasone 17-valerate (betamethasone).. The ear receiving repeated applications of oxazolone exhibited erythema, oedema and abrasion. Both preventive and therapeutic administration of olopatadine (10 mg kg(-1) day(-1)) significantly inhibited the ear swelling and the increased production of interleukin (IL)-4, IL-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor. In the histopathological analysis, olopatadine ameliorated epidermal hyperplasia and infiltration of inflammatory cells. Consistent with these results, olopatadine significantly reduced the increased expression of interferon-gamma and IL-4 mRNA. Although betamethasone (0.012 mg ear(-1) day(-1)) showed similar activities to olopatadine against these responses, it caused atrophy of the ear skin.. These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Cytokines; Dermatitis, Contact; Dibenzoxepins; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nerve Growth Factor; Olopatadine Hydrochloride; Oxazolone; RNA, Messenger

Olopatadine hydrochloride is an H1-receptor-blocker but has other anti-allergic pharmacological potencies. We investigated whether olopatadine inhibits murine contact hypersensitivity, focussing on its modulatory action on epidermal Langerhans cells serving as antigen-presenting cells. While BALB/c mice were sensitized and challenged epicutaneously with hapten, they were administered intraperitoneally with olopatadine. Olopatadine at 1 or 0.2 mg/kg of weight significantly suppressed the sensitivity when injected at least once before sensitization or challenge. In olopatadine-injected mice, the ability of Langerhans cells to present hapten to primed T cells was reduced with decreased expression of MHC class II and co-stimulatory molecules. Langerhans cells exposed in vitro to 10(-5) or 10(-6) M olopatadine had less antigen-presenting activity than control, whereas neither T cell proliferation nor keratinocyte production of IL-1alpha and IP-10 was affected at these doses. These findings suggest that olopatadine downmodulates contact hypersensitivity at least partly by interfering with the antigen-presenting ability of Langerhans cells.

Topics: Animals; Anti-Allergic Agents; Antigen Presentation; Antigens, Surface; Cells, Cultured; Chemokine CXCL10; Dermatitis, Contact; Dibenzoxepins; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Epidermis; Female; Haptens; Histocompatibility Antigens Class II; Interleukin-1; Keratinocytes; Langerhans Cells; Mice; Mice, Inbred BALB C; Olopatadine Hydrochloride; T-Lymphocytes