Table 1.
Evaluated Cytokines, Soluble Cytokine Receptors, IRS and CIRS-Related Profiles, and IRS vs CIRS Activity Ratios
| Evaluated Indices | IRS, CIRS, IRS vs CIRS Function | Controls | MDD | p-value | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Totala (N=60) | Femalesb (N=32) | Malesc (N=28) | Totald (N=100) | Femalese (N=60) | Malesf (N=40) | a vs d | b vs e | c vs f | e vs f | ||
| Cytokines | |||||||||||
| IL-1α (pg/mL) | IRS | 0.26 (0.19–0.35) | 0.27 (0.20–0.35) | 0.25 (0.18–0.33) | 0.26 (0.19–0.40) | 0.25 (0.19–0.33) | 0.26 (0.21–0.51) | 0.774 | 0.531 | 0.278 | 0.229 |
| IL-1β (pg/mL) | IRS | 1.17 (0.87–1.93) | 1.39 (0.96–2.12) | 1.09 (0.80–1.81) | 1.37 (1.00–2.04) | 1.41 (1.02–2.17) | 1.21 (0.98–1.69) | 0.237 | 0.517 | 0.428 | 0.216 |
| IL-2 (pg/mL) | IRS | 2.50 (1.50–5.22) | 2.88 (1.73–5.26) | 2.22 (1.41–3.31) | 2.34 (1.60–4.06) | 2.60 (1.82–4.06) | 1.98 (1.49–3.93) | 0.880 | 0.612 | 0.945 | 0.195 |
| IL-4 (pg/mL) | CIRS | 2.08 (1.84–2.73) | 2.29 (1.87–2.79) | 1.98 (1.80–2.41) | 2.34 (2.02–2.67) | 2.33 (2.01–2.82) | 2.36 (2.07–2.63) | 0.046 | 0.354 | 0.044 | 0.827 |
| IL-6 (pg/mL) | IRS | 0.79 (0.63–1.24) | 0.84 (0.69–1.29) | 0.69 (0.57–1.14) | 0.92 (0.69–1.19) | 0.98 (0.76–1.31) | 0.88 (0.63–1.07) | 0.319 | 0.594 | 0.345 | 0.132 |
| IL-8 (pg/mL) | IRS | 3.99 (3.04–5.91) | 3.89 (2.83–5.91) | 4.05 (3.59–5.58) | 3.31 (2.58–5.21) | 3.47 (2.51–5.10) | 3.22 (2.63–5.38) | 0.087 | 0.319 | 0.126 | 0.872 |
| IL-10 (pg/mL) | CIRS | 0.77 (0.58–0.99) | 0.79 (0.64–0.94) | 0.70 (0.54–1.02) | 0.95 (0.70–1.44) | 0.99 (0.68–1.49) | 0.94 (0.73–1.31) | <0.001 | 0.017 | 0.007 | 0.952 |
| IFN-γ (pg/mL) | IRS | 0.42 (0.28–0.56) | 0.46 (0.31–0.66) | 0.34 (0.21–0.53) | 0.45 (0.30–0.79) | 0.44 (0.28–0.82) | 0.45 (0.31–0.76) | 0.161 | 0.993 | 0.052 | 0.759 |
| TNF-α (pg/mL) | IRS | 2.46 (2.00–2.96) | 2.29 (1.78–2.83) | 2.74 (2.21–3.14) | 2.89 (2.29–3.42) | 2.84 (2.16–3.19) | 3.12 (2.63–3.47) | 0.002 | 0.006 | 0.074 | 0.064 |
| Soluble cytokine receptors | |||||||||||
| sIL-6R (ng/mL) | IRS | 0.91 (0.52–1.42) | 0.98 (0.57–1.58) | 0.90 (0.46–1.36) | 1.33 (0.87–1.80) | 1.34 (0.91–1.81) | 1.32 (0.65–1.79) | 0.004 | 0.062 | 0.035 | 0.616 |
| sTNF-R1 (ng/mL) | CIRS | 0.48 (0.39–0.59) | 0.42 (0.37–0.55) | 0.54 (0.44–0.69) | 0.49 (0.44–0.57) | 0.48 (0.42–0.55) | 0.51 (0.47–0.63) | 0.400 | 0.198 | 0.956 | 0.015 |
| sTNF-R2 (ng/mL) | CIRS | 0.44 (0.23–0.69) | 0.38 (0.22–0.69) | 0.48 (0.27–0.69) | 0.54 (0.38–0.73) | 0.52 (0.37–0.70) | 0.59 (0.47–0.77) | 0.065 | 0.178 | 0.177 | 0.156 |
| Profiles | |||||||||||
| IL-6 trans signaling | IRS | −0.20±0.23 | −0.27±0.21 | −0.10±0.49 | 0.23±0.20 | 0.43±0.27 | −0.08±0.28 | 0.304 | 0.656 | 0.998 | 0.997 |
| M1 signaling | IRS | −0.52 (−2.17–1.36) | −0.42 (−1.76–1.59) | −1.80 (−2.32–0.22) | 0.06 (−1.52–1.43) | 0.24 (−1.35–1.85) | −0.11 (−1.51–1.09) | 0.054 | 0.309 | 0.086 | 0.421 |
| Th1 profile | IRS | −0.03±0.23 | 0.39±0.30 | −0.47±0.34 | 0.04±0.16 | 0.07±0.21 | −0.01±0.24 | 0.800 | 0.998 | 0.997 | 0.996 |
| Treg+Th2 | CIRS | −0.36 (−1.34–0.24) | −0.17 (−1.09–0.53) | −0.74 (−1.74– − 0.23) | 0.28 (−0.80–1.21) | 0.22 (−0.97–1.33) | 0.28 (−0.54–0.80) | <0.001 | 0.074 | <0.001 | 0.549 |
| allIRS | IRS | −1.04±0.46 | −0.38±0.56 | −1.80±0.74 | 0.17±0.36 | 0.43±0.48 | −0.21±0.55 | 0.045 | 0.996 | 0.449 | 0.998 |
| allCIRS | CIRS | −0.57±0.25 | −0.56±0.35 | −0.58±0.37 | 0.30±0.15 | 0.22±0.20 | 0.41±0.23 | 0.002 | 0.230 | 0.111 | 0.997 |
| Ratios | |||||||||||
| TNF-α/sTNF-Rs | IRS vs CIRS | −0.53±0.24 | −0.46±0.33 | −0.62±0.34 | 0.05±0.14 | 0.12±0.17 | −0.05±0.23 | 0.029 | 0.598 | 0.852 | 0.998 |
| TNF-α/sTNF-R1 | IRS vs CIRS | −0.19 (−0.58–0.38) | 0.03 (−0.45–0.72) | −0.47 (−0.75− −0.09) | 0.04 (−0.48–0.48) | −0.01 (−0.36−0.49) | 0.07 (−0.58–0.48) | 0.159 | 0.970 | 0.047 | 0.823 |
| TNF-α/sTNF-R2 | IRS vs CIRS | 0.06±0.17 | 0.03±0.25 | 0.09±0.23 | 0.16±0.09 | 0.12±0.12 | 0.23±0.14 | 0.523 | 0.979 | 0.958 | 0.950 |
| Th1/Th2 | IRS vs CIRS | −0.15 (−1.05–0.99) | 0.47 (−1.03–1.23) | −0.23 (−1.18–0.68) | −0.36 (−1.23–0.69) | −0.27 (−0.94–0.70) | −0.44 (−1.23–0.67) | 0.496 | 0.369 | 0.958 | 0.998 |
| Th1/Treg | IRS vs CIRS | 0.28±0.21 | 0.67±0.32 | −0.15±0.25 | −0.18±0.13 | −0.11±0.17 | −0.28±0.22 | 0.051 | 0.085 | 0.996 | 0.998 |
| Th1/Treg+Th2 | IRS vs CIRS | 0.10 (−0.73–1.40) | 0.57 (−0.77–1.51) | −0.03 (−0.69–0.74) | −0.49 (−0.73–1.40) | −0.48 (−1.25–0.60) | −0.61 (−1.24–0.78) | 0.011 | 0.053 | 0.076 | 0.784 |
| M1/Th2 | IRS vs CIRS | −0.52±0.31 | −0.42±0.37 | −0.63±0.52 | −0.04±0.21 | 0.24±0.27 | −0.47±0.34 | 0.268 | 0.997 | 0.998 | 0.729 |
| M1/Treg | IRS vs CIRS | 0.03±0.30 | 0.18±0.35 | −0.17±0.53 | 0.18±0.22 | 0.30±0.27 | −0.01±0.37 | 0.710 | 0.995 | 0.992 | 0.998 |
| M1/Treg+Th2 | IRS vs CIRS | 0.11±0.30 | 0.00±0.32 | −0.22±0.48 | 0.01±0.20 | 0.09±0.26 | −0.28±0.28 | 0.973 | 0.998 | 0.997 | 0.998 |
| allIRS/allCIRS | IRS vs CIRS | −0.48±0.38 | 0.04±0.50 | −1.13±0.54 | −0.35±0.33 | 0.30±0.43 | −1.27±0.47 | 0.908 | 0.998 | 0.998 | 0.072 |
Notes: Values are expressed as mean±SEM for Gaussian-distributed data and as median (interquartile ranges) for non-Gaussian distributed data. p-value ≤ 0.05 (in bold) is considered statistically significant. aControl group; bControl adolescent females; cControl adolescent males; dDepressive group; eDepressive adolescent females; fDepressive adolescent males.
Abbreviations: IRS, inflammatory response system; CIRS, compensatory immune response system; MDD, major depressive disorder; IL, interleukin; IFN-γ, interferon-gamma; TNF-α, tumor necrosis factor-alpha; sIL-6R, soluble interleukin-6 receptor; sTNF-R1, soluble tumor necrosis factor receptor 1; sTNF-R2, soluble tumor necrosis factor receptor 2; M1, macrophages M1; Th1, T helper cells 1; Treg, T regulatory cells; Th2, T helper cells 2; allIRS, all indices involved in the adolescent depression-linked inflammatory response system; allCIRS, all indices involved in the compensatory immune response system; sTNF-Rs, soluble tumor necrosis factor receptors (ie sTNF-R1+sTNF-R2).