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Spyridon E. Chalkiadakis, Evangelia Zampeli, Ekaterini Tiligada; Histamine H4 Receptors Mediate Systemic Effects in the Rat Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2011;52(14):468.
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Conjunctival disorders have major impact on individual quality of life, while many current treatments are beset with side effects. The H4 histamine receptor (H4R) is a promising target for the development of novel anti-inflammatory approaches. This study aimed to examine the effects of the systemic administration of the H4R antagonist JNJ7777120 in the conjunctiva in a rat model of adjuvant arthritis (AA).
Male Wistar rats (200-250g bw) received 0.1ml normal saline i.p. (normal) or 0.1ml complete Freund’s adjuvant (CFA, Sigma, USA) i.d. at the base of the tail at day 0 (AA). JNJ7777120 (RL Thurmond, J&J, CA, USA) was administered i.p. at 10mg/kg to normal and AA animals. At day 20, animals were sacrificed by decapitation, the conjunctivae were removed and histamine levels were quantified fluorometrically. The results were expressed as mean±SEM (n=7). Significant differences were determined by non-parametric statistical analyses and Anova.
AA animals developed signs of arthritis in the paws in contract to their normal littermates. No abnormal clinical signs were observed in the eyes of any group. Conjunctival histamine content tended to increase in AA compared to normal tissues, yet without reaching statistical significance (p>0.05). JNJ7777120 did not significantly modify normal conjunctival histamine content (p>0.05). However it induced statistically significant reductions in the conjunctival histamine levels from 1.8±0.3ng/mg to 0.8±0.1ng/mg (p <0.05) in CFA-challenged animals.
Systemic administration of JNJ7777120 did not exert significant effects in normal conjunctival histamine levels in contrast to the previously reported increases upon local JNJ7777120 instillation. Interestingly however, systemic H4R blockade induced significant reductions in conjunctival histamine content in AA. The results point to a differential automodulatory role of the H4R in the conjunctiva under normal and systemic inflammation conditions.
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