Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome.
To explore the pathogenic mechanisms involved in adenovirus infection, we evaluated total levels of immunoglobulins, antiadenovirus antibodies, adenovirus-specific circulating immune complexes, and cytokines in serum samples obtained from 38 hospitalized children with adenovirus infection. According to their clinical findings and outcome, the infections were classified as follows: (1) moderate (group I, n = 10), (2) severe (group II, n = 12), and (3) fatal (group III, n = 16). About 60% of the children had elevated IgM levels. IgG-containing adenovirus-specific circulating immune complexes were initially detected in 7 of 16 group III patients, 4 of whom had low serum levels of the third component of complement. A decrease in initial antiadenovirus IgG antibodies was observed in 3 of 10 patients in group III. Serum interleukin-6 was not detected in group I (none of 10), but was present in group II (7 of 12, p = 0.016) and group III (13 of 16, p < 0.001). Interleukin-8 was detected in all groups; values in fatal cases were significantly higher than in surviving children. Tumor necrosis factor alpha was not observed in group I (none of 10) and was uncommon in group II (2 of 12) but was frequently detected in group III (9 of 15, p = 0.01). Interleukin-1 and interleukin-4 were rarely detected in serum samples. Increased concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were associated with hypoperfusion, febrile peaks, tonic-clonic seizures, and septic shock. In 5 of 10 patients in groups II and III, autoantibodies specific for smooth muscle were found. Our findings indicate that high serum values for interleukin-6, interleukin-8, and tumor necrosis factor alpha are associated with severity of adenovirus infection.
Mistchenko
A S
AS
Laboratorio de Virología, Hospital de Niños, Ricardo Gutiérrez, Buenos Aires, Argentina.
Diez
R A
RA
Mariani
A L
AL
Robaldo
J
J
Maffey
A F
AF
Bayley-Bustamante
G
G
Grinstein
S
S
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000401:mortality; D000260:Adenoviruses, Human / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007378:Interleukins / Q000097:blood*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000914:Antibodies, Viral; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha