heroin and Inflammation

Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy.. This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]).. A total of 120 participants were enrolled. The unadjusted mean difference in aortic TBR was 0.43 between HIV-positive [HIV+] heroin+ and HIV+ heroin-negative [heroin-] (P = .02); however, among HIV-, aortic TBR was similar regardless of heroin-use status. Further, HIV-by-heroin-use status interaction was significant (P = .02), indicating that the relationship between heroin use and higher aortic TBR depended on HIV status. On the other hand, both HIV (1.54 vs 1.68; P = .04, unadjusted estimated means for HIV+ vs HIV-) and heroin use were associated with lower bone marrow SUV, although the effect of heroin depended on sex (heroin-use-by-sex interaction, P = .03). HIV-by-heroin-use interaction was not significant for splenic or bone marrow SUV.. Aortic inflammation was greatest in PWH who use heroin, but paradoxically, bone marrow activity was the least in this group, suggesting complex and possibly divergent pathophysiology within these different end organs.

Topics: Adult; Cross-Sectional Studies; Fluorodeoxyglucose F18; Heroin; HIV; HIV Infections; Humans; Inflammation; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals

Altered gut integrity is central to HIV-related immune activation. Opioids may promote similar changes in gut permeability and/or increase systemic inflammation, potentially augmenting processes already occurring in people with HIV (PWH).. Urban hospital systems in Cleveland, Ohio, and surrounding communities.. This is a prospectively enrolled, cross-sectional study including people with and without HIV using heroin and people with and without HIV who have never used heroin, matched by age, sex, and CD4+ T-cell count (PWH only) to compare markers of gut integrity, microbial translocation, systemic inflammation, and immune activation.. A total of 100 participants were enrolled. Active heroin use was associated with higher concentrations of lipopolysaccharide-binding protein (LBP), beta-D-glucan (BDG), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor-α-receptors I and II, soluble CD163, inflammatory monocytes, and activated CD4+ lymphocytes in adjusted models. HIV status tended to modify the effect between heroin use and LBP, BDG, hsCRP, patrolling monocytes, and activated CD4+ lymphocytes (P < 0.15 for interactions); however, it was not as expected. The effect of heroin on these markers (except patrolling monocytes) was greatest among those without HIV rather than among those with HIV.. Heroin use is associated with heightened microbial translocation, systemic inflammation, and immune activation. Concurrent HIV infection in virologically suppressed individuals does not seem to substantially worsen the effects heroin has on these markers.

Topics: Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Heroin; HIV Infections; Humans; Inflammation

Drug withdrawal elicits immune responses that contribute to the development of withdrawal symptoms and relapse. The understanding of the immunologic dynamics after drug withdrawal is limited, precluding the finding of promising immune intervention measures. Here, we performed cytokine and multiplex immune profiling in heroin, methamphetamine (METH) and ephedrine users after withdrawal and identified the correlation between cytokines and other immune parameters. We showed that broad and strong inflammatory responses occurred at the early stage after drug withdrawal, and the inflammatory responses showed a downtrend with the extension of withdrawal time. Notably, immune dysregulation remained through and may last longer than 12 months after withdrawal in heroin and METH users. Our findings suggest that cytokines, immune cells, complement and immunoglobulin form a complex immune network that regulates immune responses after withdrawal. These data provide a reference for future scientific research and drug research and development.

Topics: Cytokines; Drug Users; Heroin; Humans; Inflammation; Male; Methamphetamine; Substance Withdrawal Syndrome

Intravenous drug users (IDUs) eventually encounter a common problem- a need to turn to a new vessel to inject drugs. Whether it is because no other spot is available due to scarring or convenience, the groin is the preferred spot for some. Chronic puncture of femoral vessels can lead to a rare but significant complication- femoral artery pseudoaneurysm (FAP). Its fatal consequence- rupture and bleeding is well recognized, but the forensic literature on this subject is limited. We present eight cases of exsanguination due to the ruptured FAP in IDUs who share most or all the following characteristics: long-term heroin use and/or pronounced drug use stigmata, chronic groin injection-related lesions, absence of significant precipitating pseudoaneurysm trauma, and no or minimal concentrations of heroin metabolites in blood. The FAP presentation varied greatly, from palpable fist-sized mass or slight elevation under the skin defect to infundibular arterio-cutaneous fistula that ruptured through the skin induration. In some, surrounding skin or soft tissue showed signs of inflammation but without suppuration. The most prominent FAP characteristic was smooth-surface cavitation on cross-sections. We performed microscopic evaluation in two cases and verified disruption of the artery wall (i.e., pseudoaneurysm) with elements of acute and chronic inflammation and fibrosis; foci of fibrinoid necrosis were noticed on the arterial wall. All subjects were pale, with faint hypostasis and organ anemia, consistent with reported massive hemorrhage. Because such sudden, unwitnessed, and suspicious deaths may raise the question of injury infliction, proper autopsy evaluation is crucial, for which we propose guidelines.

Topics: Aneurysm, False; Exsanguination; Femoral Artery; Groin; Hemorrhage; Heroin; Humans; Inflammation; Rupture; Substance Abuse, Intravenous

To compare the neurocognitive scores between persons living with human immunodeficiency virus (PLWH) and persons without human immunodeficiency virus (HIV) and assess the relationship between neurocognition, HIV status and variables, inflammation, and body composition measures. Cross-sectional study involving 225 participants (126 PLWH on antiretroviral therapy [ART] and 99 persons without HIV). For the first time in HIV, we used Cognivue®, an food and drug administration (FDA)-approved computer-based test to assess cognitive function. The test was calibrated to individuals' unique cognitive ability and measured 6 cognitive domains and 2 performance parameters. Markers of inflammation, immune activation, insulin resistance, and body fat composition (using dual-energy X-ray absorptiometry scan) were collected. Classical t tests, chi-square tests, and spearman correlations were used to compare and explore relationships between variables. Inverse probability weighting adjusted average treatment effect models were performed to evaluate the differences between PLWH and persons without HIV, adjusting for age, race, sex, and heroin use. Overall, 64% were male, 46% were Black, with a mean age of 43 years. Among PLWH, 83% had an undetectable HIV-1 RNA level (≤20 copies/mL). Compared persons without HIV, PLWH performed poorer across 4 domains: visuospatial (P = .035), executive function (P = .029), naming/language (P = .027), and abstraction (P = .018). In addition, PLWH had a significantly longer processing speed time compared to controls (1686.0 ms vs 1606.0 ms [P = .007]). In PLWH, lower cognitive testing domain scores were associated with higher inflammatory markers (high sensitivity C-reactive protein [hsCRP]) and with higher total fat and visceral adipose tissue (P < .05). Neurocognitive impairment (NCI) in HIV is associated with inflammation and total and central adiposity.

Topics: Adiposity; Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Female; Heroin; HIV Infections; Humans; Inflammation; Male; Obesity; RNA

Acute disseminated encephalomyelitis (ADEM) is an immune demyelinating central nervous system (CNS) disorder, characterized by monophasic new onset neurological symptoms including encephalopathy, combined with neuroradiological evidence of multifocal demyelination. ADEM is extremely rarely diagnosed and is much more common in children and adolescents than in adults. The aim of this study is to present an extremely rare case of ADEM in a heroin-addicted patient with a very difficult diagnostic course. The results of the magnetic resonance imaging (MRI) examination in this patient were inconclusive. Fungal abscesses or inflammatory lesions of an unclear nature were suspected especially in a patient with impaired immunodeficiency. In view of the constantly deteriorating condition of the patient with disturbed consciousness and the unclear aetiology, the lack of effective treatment, a decision was made to perform a bilateral stereotactic biopsy and aspiration of brain abnormalities in order to obtain a neuropathological specimen and begin with the causal treatment. Neuropathological examination revealed the presence of Creutzfeldt-Peters cells characteristic of ADEM. Treatment with methylprednisolone significantly improved the patient's general and neurological condition. To our knowledge, the above case is the first in the world literature in which ADEM has been confirmed by bilateral stereotaxic aspiration for the treatment of symptoms of increased intracranial pressure as a lifesaving procedure. Neuropathological confirmation allowed for the implementation of appropriate treatment, which resulted in complete recovery. Moreover, this case is interesting because ADEM was diagnosed in a patient addicted to heroin, where opportunistic inflammation of a fungal aetiology was considered in the first place.

Topics: Acute Disease; Adolescent; Adult; Child; Encephalitis; Encephalomyelitis, Acute Disseminated; Heroin; Humans; Inflammation; Magnetic Resonance Imaging

Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB)

Topics: Acetamides; Analgesics; Analgesics, Opioid; Animals; Arachidonic Acid; Arachidonic Acids; Carbamates; Carrageenan; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Endocannabinoids; Glycerides; Heroin; Hydrolysis; Hyperalgesia; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphine; Neuralgia; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Sciatic Nerve; Self Administration

Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles.. A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy.. These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.

Topics: Adult; B-Lymphocytes; CD40 Ligand; Comorbidity; Cross-Sectional Studies; Female; Hepatitis C; Heroin; HIV Antibodies; HIV Infections; Humans; Immunity, Humoral; Immunoglobulin G; Immunoglobulin M; Inflammation; Interleukin-8; Male; Narcotics; New York; Substance Abuse, Intravenous; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha; Young Adult

Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

Topics: Adult; Case-Control Studies; Female; Heroin; Heroin Dependence; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Tumor Necrosis Factor-alpha

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes.. This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between inflammatory pain and opioid abuse liability, and should help to facilitate the development of novel and safer opioid-based strategies for treating chronic pain.

Topics: Action Potentials; Analgesics, Opioid; Animals; Conditioning, Operant; Disease Models, Animal; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Excitatory Amino Acid Antagonists; Glycine Agents; Heroin; Hyperalgesia; Inflammation; Inhibitory Postsynaptic Potentials; Male; Neurons; Pain; Pain Threshold; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Strychnine; Sucrose; Ventral Tegmental Area

Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases); immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins) IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387). Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression.

Topics: Biomarkers; Brain; Cytokines; Female; Gene Expression Regulation; Heroin; Humans; Inflammation; Male; Molecular Chaperones

We report a 30-year-old man who developed painful swelling of his right leg and complete sciatic nerve palsy after an i.v. injection of heroin. Excessive elevation of serum creatine phosphokinase indicated the presence of rhabdomyolysis. Fasciotomy of the gluteus maximus led to rapid and complete recovery from sciatic nerve palsy. Nontraumatic rhabdomyolysis may cause a gluteal compartment syndrome that requires immediate fasciotomy.

Topics: Adult; Buttocks; Heroin; Humans; Inflammation; Injections, Intravenous; Leg; Male; Paralysis; Peripheral Nervous System Diseases; Rhabdomyolysis; Sciatic Nerve; Substance-Related Disorders; Syndrome

A case is described of a young man who presented with acute pulmonary edema and flaccid paralysis of the right upper and lower extremity, following his first injection of heroin and was found in a comatose state. Needle electromyographic findings were compatible with a severe lesion of the right brachial plexus and a moderate lesion of the right lumbar plexus. An allergic or a hypersensitivity reaction might have been the possible cause.

Topics: Acute Disease; Adult; Brachial Plexus; Drug Hypersensitivity; Heroin; Humans; Inflammation; Lumbosacral Plexus; Male; Paralysis; Pulmonary Edema

A case of bilateral necrotizing scleritis due to Aspergillus oryzae is reported. The patient was a former addict of intravenous narcotics treated five years previously for meningitis due to the same organism. A seeding focus in the thoracic spine was eventually found. The patient responded well to combined local and systemic therapy with amphotericin B, flucytosine, and natamycin. This represents, to the best of our knowledge, both the first reported case of ocular disease due to this species of Aspergillus and of isolated scleral, nonintraocular involvement in endogenous oculomycosis.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus oryzae; Child; Cocaine; Eye Diseases; Female; Flucytosine; Heroin; Humans; Inflammation; Injections, Intravenous; Meningitis; Natamycin; Sclera; Substance-Related Disorders

Candida endophthalmitis after intravenous heroin is described. Our patient had an initial rapid deterioration on systemic corticosteroids. Systemic amphotericin B, 5 flucytosine, vitrectomy and retinal surgery were required to achieve a final visual acuity of 6/24. The difficulty of an early diagnosis and the deleterious effect of corticosteroid use are emphasized.

Topics: Adult; Candidiasis; Eye Diseases; Heroin; Humans; Inflammation; Injections, Intravenous; Male; Substance-Related Disorders

Topics: Abdomen, Acute; Aneurysm, Infected; Contracture; Diagnosis, Differential; Femoral Artery; Gastrointestinal Diseases; Hand; Heart Valve Prosthesis; Heroin; Humans; Inflammation; Injections, Intravenous; Skin Diseases, Infectious; Substance-Related Disorders; Surgical Procedures, Operative; Tetanus; Thrombophlebitis

Topics: Adult; Amphetamine; Aspergillosis; Cannabis; Eye Diseases; Heroin; Humans; Inflammation; Injections, Intravenous; Lysergic Acid Diethylamide; Male; Methylphenidate; Morphine Dependence; Mycoses; Substance-Related Disorders