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16465

Toll-Like Receptor Levels and Caffeine Responsiveness In Rat Pups During Perinatal Period

Friday, October 19, 2012
Room R02-R05 (Morial Convention Center)
Turan Tunc1, Gokhan Aydemir2, Abdulbaki Karaoglu1, Ferhat Cekmez3, Mustafa Kul4, Secil Aydinoz4, Oguzhan Babacan1, Halil Yaman1 and Umit Sarici1, (1)Gulhane Military Medical Academy, Ankara, Turkey, (2)Deparment of Pediatrics, GATA Haydarpasha Teaching Hospital, Istanbul, Turkey, (3)Neonatology, GATA Medical Faculty, Ankara, Turkey, (4)Pediatrics, GATA Haydarpasa Teaching Hospital, Istanbul, Turkey

Purpose: Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. The principle risk factors in the pathogenesis of BPD are lung immaturity, mechanical ventilation, oxidative stress, prenatal and nosocomial infections. However the exact pathogenetic mechanism of lung injury and repair are incompletely understood. Toll-like receptors (TLRs) are a family of intracellular and extracellular receptors that recognize specific pathogen associated molecular patterns. Toll-like receptor expressions increase throughout development in multiple species and can be induced by agonists, cytokines, and environmental stresses to the mature immune system. In the mature lung, TLRs and other cofactors expressed on alveolar macrophages the pulmonary epithelium, and other lung cells signal effectors pathways to induce and release multiple components of the primary inflammatory response. The aim of this study is to examine the effect of caffeine, the drug used for apnea of prematurity and recently has shown beneficial effects on preterm lung, on the levels of TLR2, 4 and 9 in neonatal rat lung.   

Methods: Twenty-four pubs of three time-mated Sprague-Dawley pregnant rats were were studied as follows: Group I (control at day 0, n=8); Group II (control at day 10, n=8); Group III (Study Group, n=8). Group I was sacrificed immediately after birth. Starting from day 1 until day 10, group II received breast milk and distilled water; group III received breast milk and 20 mg/kg/day caffeine. Enzyme-linked immunosorbent assay was used to determine the tissue TLR2, TLR4 and TLR9 concentrations.

Results: There were no significant difference between groups for TLR2 and 4 levels (p>0.05). However, there was a significant difference between groups for TLR9 levels (p<0.05). Toll-like receptor 9 levels in Group III were significantly higher than Group I and II but there was no significant difference between Group I and II.

Conclusion: We speculate that the beneficial effect of caffeine on BPD might be associated with increased level of TLR9 in lung tissue. This is the first study examining the effect of caffeine treatment on levels of TLR2, 4 and 9 in newborn lung in the literature. Further studies investigating the administration of caffeine in a BPD model may contribute to better understanding the role of TLRs in the pathogenesis of BPD.