Newborn patients exhibit an unusual pattern of interleukin 10 and interferon gamma serum levels in response to cardiac surgery.

OBJECTIVE: The aim of this study was to determine the clinical significance of serum levels of interleukin 10 and interferon gamma in pediatric patients undergoing cardiopulmonary bypass. METHODS: We divided the patients into 2 groups: 8 neonates and 19 non-newborn children. Interleukin 10 and interferon gamma serum levels were quantified before sternotomy, at admission to the pediatric intensive care unit (30 minutes postoperatively), 24 hours after the onset of the operation, and 3 days after the operation. RESULTS: Newborn patients displayed significantly greater amounts of serum interleukin 10 than older children, not only in regard to the peak level achieved but also at every postoperative time point analyzed. In contrast, no significant changes in interferon gamma serum levels were observed in neonates at any time point, whereas non-newborn pediatric patients showed a significant increase in interferon gamma serum concentrations immediately after the operation. This unusual pattern of cytokine response in newborn patients was not associated with modifications in cortisol serum levels. Furthermore, although neonates had significantly different surgical and clinical variables than did the non-newborn pediatric patients, the variation in interleukin 10 production in neonates could not be accounted for by differences in the magnitude of surgical injury. In the group of neonates, there were significant positive correlations between peak interleukin 10 serum levels and both partial pressure of arterial oxygen/fraction of inspired oxygen ratio and postoperative body weight gain. CONCLUSIONS: Newborn patients undergoing cardiopulmonary bypass exhibit a distinctive biologic response pattern characterized by high levels of serum interleukin 10 without changes in serum interferon gamma. This cytokine imbalance could have potential clinical implications.

Characterization of antibody responses to annual influenza vaccination over four years in a healthy elderly population.

The effects of yearly influenza immunization on the level of antibody responses were assessed in 92 healthy elderly subjects immunized over four contiguous years (1993-1996) with a trivalent influenza vaccine that included A/Texas annually. Anti-A/Texas antibodies increased significantly and similarly post-vaccination each year, but returned to comparable baseline levels annually. Percentages of subjects with anti-A/Texas titers > or =40 post-vaccination were comparable over four years. Importantly, post-vaccination titers > or =40 to A/Texas in 1993-1994 predicted anti-A/Texas titers > or =40 in subsequent years. Thirty percent of individuals produced four-fold rises to any vaccine component the first year it was included in the vaccine, however, this percentage decreased to about 10% after subsequent vaccination with the same component. This study clearly supports the concept that annual immunization with the same influenza vaccine component over multiple years does not significantly decrease antibody titers in a healthy elderly population.

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc.

Immunity and nutritional status are compromised with age, yet the relationship between them is unclear. Immune responses and plasma micronutrient levels of 61 healthy elderly (mean 81 years) and 27 young (mean 27 years) were assessed before and after immunization with trivalent influenza vaccine (FLU). FLU-induced proliferation and IFN-gamma levels of elderly were lower than young before and after immunization. Proliferation and IFN-gamma levels increased after immunization of young, but not elderly. FLU-induced IL-6 and IL-10 levels did not change after immunization of either group. While antibody titers to all three FLU components increased after vaccination of young and elderly, post-vaccination titers of elderly were lower than young. Although plasma retinol and zinc levels of young and elderly were similar before and after vaccination, elderly had higher plasma beta-carotene and alpha-tocopherol levels at both assessments that increased after vaccination. Importantly, plasma micronutrient levels were comparable for elderly with or without intact (titers >/=40 and fourfold rise post-vaccination) antibody responses after vaccination. These results suggest that differences in these plasma micronutrients (1) are not required to observe decreased FLU responses of healthy elderly compared to young and (2) are not associated with differences in antibody responses among healthy elderly.

Liposomal amphotericin B and amphotericin B-deoxycholate show different immunoregulatory effects on human peripheral blood mononuclear cells.

Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.

Cytokine production after influenza vaccination in a healthy elderly population.

Influenza vaccination is less efficacious in the elderly than in the young. To characterize this age-related decrease in immune response to influenza vaccination, antibody and cell-mediated responses to influenza vaccine were assessed before immunization and 4 weeks after vaccination of a population of 270 healthy elderly individuals (mean age: 80.2 years) living in eight local continuing care retirement communities (CCRCs) and 30 young individuals (mean age: 27.8 years). The antibody titres produced against all three influenza strains increased significantly after vaccination in both the young and elderly (p < 0.0005); however, the young demonstrated significantly higher titres to all three strains than did the elderly (p < 0.03). Peripheral blood mononuclear cells (PBMC) cultured with influenza vaccine demonstrated significantly increased proliferation (elderly: p < 0.00005; young: p < 0.001) after vaccination, with proliferative responses in the young significantly higher than the elderly both before (p < 0.04) and after (p < 0.0005) vaccination. Similarly, IFN gamma production in these PBMC cultures increased significantly pre- to postvaccination in both young and elderly (young: p < 0.006; elderly: p < 0.00005), but the young produced more than the elderly both pre- and postvaccination (p < 0.0001). Following vaccination, PBMC production of IL-10 was higher in the young than in the elderly (p < 0.0015), while IL-6 production was comparable in both young and elderly individuals. Greater than 13% of the elderly population did not produce detectable IL-6, IL-10, or IFN gamma either before or after vaccination. The data show that the decreased cell-mediated and humoral responses to influenza vaccination of this healthy elderly population are accompanied by the production of lower levels of cytokines. A unique finding in this population of 270 healthy elderly was the association between a TH0 cytokine profile and intact immune responses to influenza vaccine. A similar relationship was not seen in the young.

Effect of age on cytokine production in humans.

Aging is accompanied by many changes in immune response, with the most consistent and dramatic alterations occurring within the T cell compartment. Since cytokines are central to immune cell communications, age-associated changes in cytokine production may contribute to these alterations. While data from murine studies suggest a switch from a Th1 (IL-2, IFNγ) to a Th2 (IL-4, IL-6, IL-10) cytokine response, this model has not been as clearly established in humans. In addition, this current review of over 50 studies in humans suggests that age-associated changes in cytokine production are not consistent.

The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc.

The decline in the lymphoproliferative response to mitogenic stimuli shows marked heterogeneity in elderly individuals. Adequate nutriture is required for optimal immune function, yet nutritional status may be compromised in the elderly. To address whether this variation in the proliferative response of elderly individuals is related to their nutritional status, we studied 61 elderly (80.5 +/- 5.7 year-old) and 27 young (27.3 +/- 3.8 year-old) individuals participating in an ongoing assessment of their immune response to influenza vaccine. Ambulatory elderly individuals were recruited from five different retirement communities and were in good health upon enrollment in the study. Thirty-three percent of young and 54% of elderly subjects reported consuming micronutrient supplements daily during the study. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from fasting individuals twice, 4-6 weeks apart. At both times, proliferative responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were significantly lower (P < 0.004) in the elderly compared to the young. However, at both times, elderly participants had plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc that were either significantly greater than, or equal to, those of young subjects. No significant correlations between plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc and level of proliferative responses to each stimuli were observed in elderly individuals at either time. Thus, the heterogeneity in the proliferative response to mitogenic stimuli exhibited by a healthy elderly population cannot be attributed to differences in these nutritional parameters.