interleukin-8 and Abnormalities--Multiple

Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor-alpha (TNF-α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 polymerase chain reaction was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID-19 requires further investigation.

Topics: Abnormalities, Multiple; Adolescent; Antirheumatic Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Crohn Disease; Genetic Diseases, X-Linked; Humans; Ichthyosiform Erythroderma, Congenital; Infliximab; Interleukin-6; Interleukin-8; Limb Deformities, Congenital; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tumor Necrosis Factor-alpha

Aicardi-Goutières syndrome (AGS) presents as a severe autosomal recessively inherited neurological brain disease. Clinical and neurological manifestations closely resemble those of congenital viral infection and are generally attributed to a perturbation of innate immunity including a long lasting lymphocytosis and production of interferon-alpha (IFNalpha) in the central nervous system. To clarify the innate immune response evoked in these diseases, we used a 30-mer multiplexed luminex system to measure multiple cytokines and growth factors in the cerebrospinal fluid and serum of patients with AGS and viral meningitis or encephalitis, and febrile controls in whom infection could not be substantiated. In addition to the previously described IFNalpha, both AGS and viral diseases were characterized by expression of CXCL10 and CCL2. In contrast to AGS, viral infection resulted in high levels of IL-6 and CXCL8 in the CNS. Postmortem immunohistochemical staining of brain sections showed that in both AGS and viral CNS infection, astrocytes were responsible for the production of cytokines and not the infiltrating leukocytes. In summary, our data indicate that astrocytes are the predominant cell type responsible for the production of IFNalpha and CXCL10 in AGS. Whereas IFNalpha is assumed to be involved in the neurodegeneration, calcifications and seizures in AGS, CXCL10 may act as the chemoattractant responsible for the influx of activated lymphocytes into the brain. The lack of the inflammatory cytokines IL-6 and CXCL8 in AGS suggest that the neuroinflammatory reaction in this disease is distinct from viral disease.

Topics: Abnormalities, Multiple; Adult; Aged; Astrocytes; Brain Diseases; Calcinosis; Chemokine CXCL10; Child; Child, Preschool; Encephalitis; Female; Gliosis; Humans; Infant; Infant, Newborn; Interferon-alpha; Interleukin-6; Interleukin-8; Male; Meningitis, Viral; Middle Aged; Postmortem Changes