Influence of isoniazid on T lymphocytes, cytokines, and macrophages in rats

Cao, Bianchuan; Li, Qiuju; Huang, Zhe; Huang, Xiufang; Zhu, Yihong; Xiao, Ke; Huang, Fuli; Zhong, Li

doi:10.1590/s2175-97902019000418547

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 56 • 2020 • https://doi.org/10.1590/s2175-97902019000418547 copy

Influence of isoniazid on T lymphocytes, cytokines, and macrophages in rats

Authorship SCIMAGO INSTITUTIONS RANKINGS

T lymphocytes, cytokines, and macrophages play important roles in the clearance of Mycobacterium tuberculosis (Mtb) by the immune system. This study aimed to investigate the effects of isoniazid on the functions of both innate and adaptive immune cells. Healthy rats were randomly divided into experimental and control groups. Each group was randomly divided into three subgroups and named according to the duration of drug feeding, 1, 3, and 3 months followed by drug withdrawal for 1 month. The experimental groups were fed with isoniazid (12 mg/mL) and the control groups with normal saline. The percentage of CD4⁺ and CD8⁺T lymphocytes, level of interleukin (IL)-12 and interferon (IFN)-γ, and function of macrophages were determined at these three time points. Isoniazid significantly increased the percentage of CD4⁺T lymphocytes and the CD4⁺/CD8⁺T lymphocyte cell ratio (P < 0.05). It transiently (<1 month) enhanced the functions of rat macrophages significantly (P < 0.05). In summary, isoniazid could increase the percentage of CD4+T lymphocytes, CD4⁺/CD8⁺T lymphocyte cell ratio, and enhance macrophage function in healthy rats.

Keywords:
Cytokines; Immune; Isoniazid; Macrophages; T lymphocytes

Time point	Experimental group(n=10)	Control group (n=10)	P-value
CD4⁺T lymphocytes (%)
Feeding drug for 1 month	48.332 ± 5.486	37.625 ± 4.192	0.000 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	42.169 ± 6.041	35.421 ± 7.882	0.045 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	36.656 ± 5.639	32.642 ± 5.325	0.119 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
CD8⁺T lymphocytes (%)
Feeding drug for 1 month	11.243 ± 1.572	13.642 ± 3.292	0.058 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	12.280 ± 4.398	15.611 ± 5.557	0.154 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	15.780 ± 6.048	15.963 ± 3.814	0.936 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
CD4⁺/CD8⁺ ratio
Feeding drug for 1 month	4.372 ± 0.780	2.880 ± 0.637	0.000 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	3.903 ± 1.579	2.552 ± 1.065	0.038 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	2.604 ± 0.869	2.185 ± 0.723	0.256 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference

Time point	Experimental group (n=10)	Control group (n=10)	P-value
IL-12 (pg/mL)
Feeding drug for 1 month	134.409 ± 25.128	131.752 ± 41.084	0.874 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	137.034 ± 65.937	96.211 ± 18.836	0.088 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	113.241 ± 38.698	96.019 ± 20.463	0.234 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
IFN-γ (pg/mL)
Feeding drug for 1 month	121.552 ± 21.847	107.609 ± 34.765	0.297 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	118.444 ± 8.158	127.379 ± 24.003	0.289 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	114.280 ± 18.796	105.517 ± 19.753	0.323 ^a a Two independent-sample t test. P < 0.05 denoted statistical significant difference

Time point	Experimental group (n=10)	Control group (n=10)	P-value
Carbon clearance index
Feeding drug for 1 month	0.017 ± 0.004	0.006 ± 0.001	0.000 ^a a Two independent-sample t test;
Feeding drug for 3 months	0.011 ± 0.001	0.012 ± 0.002	0.798 ^a a Two independent-sample t test;
Feeding drug for 3 months followed by drug withdrawal for 1 month	0.024 ± 0.009	0.029 ± 0.009	0.248 ^a a Two independent-sample t test;
Phagocytic index
Feeding drug for 1 month	6.383 ± 0.602	4.637 ± 0.374	0.000 ^a a Two independent-sample t test;
Feeding drug for 3 months	6.366 ± 0.578	6.377 ± 0.491	0.964 ^a a Two independent-sample t test;
Feeding drug for 3 months followed by drug withdrawal for 1 month	8.391 ± 1.526	8.142 ± 0.989	0.671 ^a a Two independent-sample t test;
Acid phosphatase level (Mean rank)
Feeding drug for 1 month	13.40	7.60	0.029 ^b b Rank-sum test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months	10.00	11.00	0.739 ^b b Rank-sum test. P < 0.05 denoted statistical significant difference
Feeding drug for 3 months followed by drug withdrawal for 1 month	11.25	9.75	0.579 ^b b Rank-sum test. P < 0.05 denoted statistical significant difference

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: L. Zhong, Department of Infectious Disease, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Luzhou, Sichuan, 646000, China. E-mail: zhongli620@163.com.