Cytokines are constitutively expressed and influence boththe development and function of the nervous system. In par-ticular, interleukin-1beta (IL1beta) has been recognized toplay an important role in normal development of the brainas a regulator of synaptic function and neuronal plasticityunderlying learning and memory. Imbalanced cytokine pro-duction, signaling, and/or regulation can therefore have awide range of neurological consequences. The cytokine'sproduction is under genetic control and polymorphismshave been identified in these genes. In intellectual disability(ID) such as already demonstrated in autism, cytokine dys-regulation could contribute to neuronal dysfunctioninfluencing cognitive development. To investigate on this,the polymorphisms of several cytokines and their serumlevels in 45 ID patients and 23 controls were studied. Wedemonstrated that IL-1beta -511 (CT) and +3962(CT) polymorphisms are involved in ID, showing a positiveassociation of CC genotype (-511 p=0.04; +3962 p=0.04)and a TT genotype negative association (-511 p=0.0009;+3962 p=0.025). The gender-related difference analysis inthe disease onset confirmed results only for the -511 poly-morphism. Specifically, the predisposing association of CCgenotype was established in the females and the protectiveone of TT genotype in the males. The gender impact wasstill more evident considering both polymorphisms. In fact,the predisposing CC-CC combination was more frequent infemales (p=0.02). Analyzing the IL-1beta serum levels,increased levels were seen in patients of both groups withpredictive CC -511 genotype (p<0.05). It is interesting tonote that the highest serum levels have been found infemales with severe ID. Overall, our results could help toidentify factors causing abnormal CNS function in childwith ID to develop correct interventions and treatments.
WHAT ROLE DOES IL-1BETA CYTOKINE PLAY IN INTELLECTUAL DISABILITY?
Aureli Anna;Sebastiani Pierluigi;Del Beato Tiziana;Di Loreto Silvia
2018
Abstract
Cytokines are constitutively expressed and influence boththe development and function of the nervous system. In par-ticular, interleukin-1beta (IL1beta) has been recognized toplay an important role in normal development of the brainas a regulator of synaptic function and neuronal plasticityunderlying learning and memory. Imbalanced cytokine pro-duction, signaling, and/or regulation can therefore have awide range of neurological consequences. The cytokine'sproduction is under genetic control and polymorphismshave been identified in these genes. In intellectual disability(ID) such as already demonstrated in autism, cytokine dys-regulation could contribute to neuronal dysfunctioninfluencing cognitive development. To investigate on this,the polymorphisms of several cytokines and their serumlevels in 45 ID patients and 23 controls were studied. Wedemonstrated that IL-1beta -511 (CT) and +3962(CT) polymorphisms are involved in ID, showing a positiveassociation of CC genotype (-511 p=0.04; +3962 p=0.04)and a TT genotype negative association (-511 p=0.0009;+3962 p=0.025). The gender-related difference analysis inthe disease onset confirmed results only for the -511 poly-morphism. Specifically, the predisposing association of CCgenotype was established in the females and the protectiveone of TT genotype in the males. The gender impact wasstill more evident considering both polymorphisms. In fact,the predisposing CC-CC combination was more frequent infemales (p=0.02). Analyzing the IL-1beta serum levels,increased levels were seen in patients of both groups withpredictive CC -511 genotype (p<0.05). It is interesting tonote that the highest serum levels have been found infemales with severe ID. Overall, our results could help toidentify factors causing abnormal CNS function in childwith ID to develop correct interventions and treatments.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
