Section 1 (Table 1):
Peripheral mechanisms in blood, including leukocytes and cytokines
| In-vivo Sample (Dx, N, age, sex) Stage in OUD |
Target | Direction of effect, compared to healthy controls | Other patient characteristics and notes | Citation |
|---|---|---|---|---|
| Males with OUD (n=48), mean age=32 Within 24 h of last opioid exposure |
Serum cytokine panel | ↑TNF-α, ↑IL-10 ↓IL-6 |
(Purohit, et al., 2022) | |
| Heroin users (n=81), mean age=35, males Abstinence periods ranged: 7 days – 12 mo |
Plasma cytokine panel (27 targets) | ↑IL-17A, ↑IL-6 ↑IL-10, ↑IL-1ra, ↑IL-4, ↑RANTES High at early abstinence, then decrease over time ↑IL-7, ↑IL-17A and other cytokines High at early abstinence and remained high |
(Re, et al., 2022) | |
| Males with OUD in acute (7–14 days; n=10) or protracted (1 year; n=21) abstinence, mean age=37 | Plasma cytokine panel | ↑IL-4, ↑G-CSF, ↑IL-7, ↑IL-10, ↑IL-17A, IL-2 In acute abstinence |
Some poly-drug use (esp. methamphetamine) Several of the cytokine changes normalized by 1 year abstinence |
(Zhang, et al., 2021) |
| Heroin IVDU (n=19), mean age=28, 68%male Injected heroin within 3 days of study |
Plasma and cellular panel | ↑TNF-α, ↑TGF-alpha, ↑IL-8 | Poly-drug use reported (e.g., cocaine). In syringe exchange program |
(Piepenbrink, et al., 2016) |
| Males with heroin addiction (n=90), age range 18–45, in buprenorphine treatment. |
Neutrophil and platelet: lymphocyte ratios | Ratios increased, indicating greater systemic inflammation | Ratios correlated with duration of addiction | (Cicek et al., 2018) |
| Males with OUD (n=20), mean age 36 In methadone maintenance. |
TNF-α levels before and in early methadone maintenance | ↑TNF-α at early abstinence, decreases over 2 weeks of methadone. | All OUD patients were also tobacco smokers | (Salarian, et al., 2018) |
| OUD patients (n=47), mean age 37, 87%males In methadone maintenance. | Plasma cytokine panel and cognitive tests over 12 weeks of MMT | Negative correlation between TNF-α levels and visual index, and IL-6 and verbal memory index | Inflammatory markers and verbal memory tended to recover during MMT. | (Wang, et al., 2018) |
| Persons with OUD (n=33), mean age= 40, 90% male Blood samples obtained at the onset of methadone maintenance, and up to 12 weeks. |
Plasma cytokine panel | ↑TNF-α, ↑TIL-8 | TNF-α levels remained elevated for at least 12 weeks of MMT. | (Chen et al., 2012) |
| Males with OUD (n=34), mean age=40. Samples obtained after at least 1 month of methadone maintenance. |
Serum cytokine panel | ↑IL-1β, ↑IL-6, ↑IL-8 |
(Chan et al., 2015) | |
| Males with OUD (n=20), age range: 21–40 | immune stimulation of blood samples. | ↑IFN-γ, ↑IL-10 Production after stimulation | Phytohemagglutinin or lipopolysaccharide stimulation | (Azarang et al., 2007) |
| Males with OUD (n=19) and in heroin withdrawal (n=17). Mean ages 22–26. | immune stimulation of blood samples. | ↓T-cell activation after stimulation in OUD. Decreases in CD4/CD8 ratios observed in early withdrawal. |
Phytohemagglutinin stimulation | (Govitrapong, et al., 1998) |
| Males with OUD (n=11 heroin users, n=11 in methadone maintenance. Mean ages ranged 29–41 | measurement of natural killer (NK) cell activity in vitro | ↓NK activity in active heroin users | Recovery of NK activity in MMT | (Novick, et al., 1989) |
| Persons with OUD (n=38), age at least 21. Sex unspecified. Recruited during admission to methadone maintenance. |
immune stimulation of blood samples in vitro. | ↓T-cell activation after stimulation. | (Brown, et al., 1974) |
Dx: diagnosis; MMT: methadone maintenance therapy