Comparative Study of the Pituitary Adrenal Axis in Cats Infected with Feline Immunodeficiency Virus (FIV)
The neuroendocrine and immune systems are bidirectionally communicated. The neuro-immune-endocrine interface is mediated by cytokines such as IL1, TNFα and IL6. These cytokines play a variety of roles in stress, behaviour; sensory processing and cognition. The immune system is partially regulated by the hypothalamus pituitary adrenal axis (HPA) and the sympathetic nervous system. Cortisol is the key effector glucocorticoid synthesized via the HPA axis. This hormone has been associated with the development of several retroviral diseases and their pathogenesis, such as Feline immunodeficiency. FIV is a lentivirus that causes a progressive disruption of the immune function in cats.
The main objective of the present study is to compare neuro-immune-endocrine parameters (ACTH, Cortisol, AGP and Evoqued potentials) in cats infected with FIV along 6 months of antiretroviral therapy.
Material and Methods
Sera and plasma of cats were analyzed for: IL1 (Elisa, Lehmann, 1992), Acute Phase Protein (Alpha-Glycoprotein acid) (Immunoprecipitation, Ecos, Japan), endogenous ACTH (RIA), and cortisol (RIA). In addition, neurological manifestations of the patients were studied through auditory and visual evoked potentials (AEP; VEP). FIV infection was confirmed by nested PCR. The samples were obtained at two times: one in the beginning of therapy and the other after six months of treatment with antiretrovirals: Zidobudine (AZT 5mg/kg/ day) and Valproic acid: 10 mg/kg/day). Statistical results were analyzed with Mann-Whitney test (p <0.05). In order to compare IL1, ACTH and AGP, Chi-Square test and Contingency tables were used. Correlation was estimated with Pearson-test.
Values are represented as median and range. Mann-Whitney test significance p<0.05. There were not significant differences in cortisol levels and there were not correlation between ACTH and cortisol. IL1 decreases significantly after 6 months of treatment (p 0.03). Correlation between IL1 vs ACTH and IL1 vs AGP was found. VEP showed latencies higher than 162 mseg in the p100 in 75% of cats. Alterations of AEP were observed only in 30% of the patients and there were not significant differences between both times of evaluation.
The results at the beginning of the therapy showed a compromise of the neuroimmune-endocrine axis. High levels of ACTH, IL1 and AGP were observed, due to chronic stress, inducing an alteration of normal regulation of the HPA axis. The comparison with the results after 6 months of treatment showed a lesser activation of axis. Positive correlation between IL1, ACTH and AGP is related to the improvement of the disease. It is well known that IL1 stimulates the axis, with other cytokines, and induces liberation of Acute Phase Proteins (AGP). The therapy, as the present results show, could produce an improvement of the disease, diminishing IL1 levels and consequently ACTH and AGP levels slow down. There were not correlation between Cortisol and ACTH levels and this could be explained because of the abnormal regulation of the axis in this patients.
Feline Immunodeficiency produced by a Retrovirus, Lentivirus, causes a similar condition to Human Immunodeficiency (AIDS) and it is being intensively studied worldwide. It is particularly relevant to study auditory and visual evoked potentials, since FIV produces a slowing down of the conduction of the nervous impulse but this al least did not showed amelioration after six month of therapy. The treatment of the disease with Zidobudine and Valproic acid during 6 months shows in the present results a normalization of HPA axis, diminishing the chronic stress.