Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids

Table 4 Effects of Tat and morphine on cytokine concentrations in the spinal cord of Tat transgenic mice that are not presented in Figs. 5 and 6

Spinal cord cytokines	Genotype	Repeated saline	Repeated morphine	Genotype effect		Drug effect		Genotype x drug
pg/mL		mean ± SEM	mean ± SEM	F_{1, 19}	p	F_{1, 19}	p	F_{1, 19}	p
Proinflammatory cytokines
IL-2	Tat(−)	12.5 ± 0.36	14.3 ± 0.47	2.3	0.15	16.9	< 0.01	< 1.0	0.98
IL-2	Tat(+)	11.8 ± 0.44	13.6 ± 0.46	2.3	0.15	16.9	< 0.01	< 1.0	0.98
IL-6	Tat(−)	3.4 ± 0.17	3.6 ± 0.19	1.5	0.24	1.5	0.23	< 1.0	0.79
IL-6	Tat(+)	3.2 ± 0.13	3.4 ± 0.19	1.5	0.24	1.5	0.23	< 1.0	0.79
IFN-γ	Tat(−)	29.1 ± 0.76	30.3 ± 0.71	< 1.0	0.38	6.2	0.02	< 1.0	0.37
IFN-γ	Tat(+)	27.8 ± 0.74	30.3 ± 0.76	< 1.0	0.38	6.2	0.02	< 1.0	0.37
TNF-α	Tat(−)	52.4 ± 1.70	51.8 ± 1.67	1.6	0.22	1.6	0.22	2.8	0.11
TNF-α	Tat(+)	47.8 ± 1.73	52.4 ± 0.48	1.6	0.22	1.6	0.22	2.8	0.11
Anti-inflammatory cytokines
IL-5	Tat(−)	3.4 ± 0.22	3.4 ± 0.12	4.3	0.05	< 1.0	0.44	< 1.0	0.36
IL-5	Tat(+)	3.2 ± 0.13	2.9 ± 0.11	4.3	0.05	< 1.0	0.44	< 1.0	0.36
IL-13	Tat(−)	40.8 ± 3.86	41.6 ± 3.27	1.6	0.21	1.7	0.20	2.4	0.14
IL-13	Tat(+)	41.7 ± 2.73	32.4 ± 2.63	1.6	0.21	1.7	0.20	2.4	0.14
Chemokines
CCL2	Tat(−)	50.8 ± 1.13	57.7 ± 1.66	2.4	0.14	12.7	< 0.01	< 1.0	0.64
CCL2	Tat(+)	48.9 ± 1.83	54.2 ± 2.24	2.4	0.14	12.7	< 0.01	< 1.0	0.64
CCL3	Tat(−)	5.1 ± 0.14	5.3 ± 0.19	3.5	0.08	< 1.0	0.71	< 1.0	0.53
CCL3	Tat(+)	4.8 ± 0.21	4.8 ± 0.21	3.5	0.08	< 1.0	0.71	< 1.0	0.53
CCL4	Tat(−)	67.4 ± 1.27	74.5 ± 0.78	1.4	0.25	20.3	< 0.01	< 1.0	0.44
CCL4	Tat(+)	66.9 ± 1.85	71.9 ± 1.18	1.4	0.25	20.3	< 0.01	< 1.0	0.44
CCL11	Tat(−)	108.4 ± 5.37	100.4 ± 4.32	< 1.0	0.57	< 1.0	0.72	1.7	0.20
CCL11	Tat(+)	99.3 ± 4.37	103.9 ± 5.01	< 1.0	0.57	< 1.0	0.72	1.7	0.20

Cytokine concentrations in the spinal cord of repeated (8-day) saline- or morphine-treated Tat(−) and Tat(+) mice. Data are expressed as mean ± SEM in pg/mL. Samples were loaded at 500 μg/mL total protein. Two-way ANOVAs for each CNS region were conducted with genotype and drug as between-subjects factors. F values and p values are presented from ANOVA results. Bolded values denote significant differences at α = 0.05; n = 5–6 mice per group. Additional cytokines and chemokines are represented in Figs. 5 and 6

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