Plasma Neopterin Levels Research Articles

Cancer cachexia and depressive states: a neuro-endocrine-immunological disease?

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophan-nicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cachexia.

NITRIC OXIDE FORMATION AS PREDICTIVE PARAMETER FOR ACUTE GRAFT-VERSUS-HOST DISEASE AFTER HUMAN ALLOGENEIC BONE MARROW TRANSPLANTATION

Due to the accumulation of evidence concerning a putative role of nitric oxide (NO) in graft-versus-host disease (GVHD), we performed follow-up measurements of the stable end-products of NO, nitrite/nitrate (NO2-/NO3-) in plasma of patients undergoing allogeneic (n = 16) and autologous (n = 6, as a control) bone marrow transplantation. NO2-/NO3- concentrations were set in relation to the clinical course and to serum levels of soluble tumor necrosis factor receptor 75 (sT-NFrec 75) and neopterin, both of which are known to be sensitive indicators of cellular immune activation phenomena involving macrophages in vivo, and endogenous interleukin (IL)-10, a major T helper cell type 2 (TH-2)-derived cytokine and potent inhibitor of macrophage activation and NO formation. A significant rise of NO2-/NO3- levels was observed in patients with GVHD and preceded the onset of clinical symptoms by up to 3 days. In contrast to indicators of macrophage activation, i.e., neopterin and sT-NFrec75, NO2-/NO3- concentrations were not significantly altered from baseline levels during infectious complications, as NO2-/NO3- concentrations did not fluctuate in patients after autologous engraftment. During episodes of acute GVHD, NO2-/NO3- concentrations showed a strong positive correlation with levels of plasma neopterin and sTNFrec 75, but were also significantly related to IL-10. In non-GVHD patients, a negative correlation between IL-10 and NO2-/NO3- concentrations was evident. Therefore, NO2-/NO3- determination may be a valuable early indicator of the initiation of human GVHD. Our results provide some further insights concerning cytokine-related metabolic changes in the course of human GVHD in vivo which may prove useful in the development of new therapeutic approaches for this disease.

Inflammatory response in peritoneal exudate and plasma of patients undergoing planned relaparotomy for severe secondary peritonitis.

To study the pattern of intraperitoneal cytokine release in secondary peritonitis and its correlation with plasma levels and prognosis. Noncomparative descriptive case series. Department of surgery in a university hospital. Seventeen consecutive patients undergoing planned relaparotomy for severe intra-abdominal infection (Acute Physiological and Chronic Health Evaluation [APACHE II] score > 10; mean score, 17.5). The following were measured at the first and last serial operations in the peritoneal exudate and plasma: endotoxin, tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), elastase, and neopterin. Survival and death. Six patients died. Peritoneal endotoxin levels were significantly higher than in the plasma and were significantly higher in the nonsurvivors. Plasma TNF-alpha, IL-6, elastase, and neopterin levels remained elevated in the nonsurvivors prior to death. Levels of TNF-alpha, IL-6, elastase, and endotoxin were 19, 993, 239, and 7 times higher, respectively, in the peritoneal exudate than in plasma, all significant differences. Elastase and TNF-alpha levels decreased in survivors during the operative treatment but remained elevated in the nonsurvivors. Secondary peritonitis is associated with a significant cytokine-mediated inflammatory response that is compartmentalized in the peritoneal cavity and indicates an adverse prognosis. Levels of cytokines in the exudate of peritonitis may be used to better stratify the severity of peritonitis and, in future, to guide local therapy.

Impaired in-vitro lymphocyte responses in patients with elevated pentachlorophenol (PCP) blood levels.

Immune parameters were examined in 188 patients who were exposed for more than 6 mo to pentachlorophenol-containing pesticides. Blood levels of pentachlorophenol, lymphocyte subpopulations, in-vitro responses to mitogenic and allogeneic stimulation, plasma neopterin levels, and plasma cytokine and cytokine receptor levels were determined. Impaired in-vitro lymphocyte stimulation responses were impaired in 65% of the patients. The likelihood of impaired lymphocyte stimulation increased significantly with levels of pentachlorophenol that exceeded 10 microliters/l (p < .05). Patients who had high blood levels of pentachlorophenol and abnormal lymphocyte stimulation also had increased proportions of blood monocytes in blood (p < .05), as well as increased IL-8 serum levels (p < .02). Eleven patients who had abnormal mitogen stimulation experienced decreased CD4/CD8 ratios of < 1.0; 5 of these patients had decreased CD4+ lymphocyte counts of < 500/microliters, and 3 patients had increased plasma neopterin of > 15 nmol/l. These results indicate that increased levels of pentachlorophenol in blood can lead to severe T lymphocyte dysfunction.

Interleukin-10 and the monocyte/macrophage-induced inflammatory response in septic shock.

Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.

Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity

The present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.

Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: Further evidence for an immune response

There is now some evidence that major depression may be accompanied by an immune response. The latter condition is suggested by elevated secretion of neopterin and interferon-γ (IFNγ) and by lower L-tryptophan ( L-TRP) plasma levels. This study investigated the plasma levels of neopterin, L-TRP, and the L-TRP/competing amino acids (CAA) ratio in 30 normal control subjects and 47 depressed subjects (16 minor depressed, 13 simple major depressed, and 18 melancholic subjects), and IFNγ secretion by mitogen-stimulated peripheral blood mononuclear cells in 7 normal control subjects and 13 major depressed subjects. Plasma neopterin levels were significantly higher in depressed subjects than in normal controls; 61% of melancholic patients had increased neopterin levels (⩾ 7 nmol/1) with a specificity of 90%. Patients with major depression had significantly lower L-TRP and L-TRP/CAA values compared with normal control subjects. The amino acid values were significantly and negatively correlated with plasma neopterin levels. Major depressed subjects exhibited significantly higher IFNγ secretion than did normal control subjects. The results further support the hypothesis that major depression is accompanied by an immune response and that the lower L-TRP availability in that illness may be an epiphenomenon of immune activation.

Hypozincemia in depression

This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.

Peripheral blood immune responses to surgically induced lung tissue injury.

Surgically induced lung tissue trauma reveals an immune response in peripheral blood, the degree of which could depend on extent and severity of the organ trauma and the presence of lung malignancies. The study included 34 patients who underwent elective thoracic surgery because of benign and malignant lung tissue diseases. Flow-cytometric phenotyping of lymphocyte subsets shows a clear shift to reduced immunocompetent cells after lung tissue injury. Patients with lung tumors reveal a postoperative activation of the macrophage system as indicated by increased plasma levels of neopterin. Increased levels of soluble interleukin-2 receptor in the plasma of these patients may be the result of cellular shedding of the receptor. Lung tissue trauma is also followed by reduced immunoglobulin levels which are most pronounced in the presence of lung malignancies. These results suggest that lung tissue injury leads to postoperative immunosuppression especially in tumor patients.

IL-6 INDEPENDENT MONOCYTE/B CELL DEFECT IN RENAL TRANSPLANT RECIPIENTS WITH LONG-TERM STABLE GRAFT FUNCTION

We showed previously that the B cell response in renal transplant recipients with long-term stable graft function (ST patients) is significantly affected by T suppressor activity. To further assess the role of the monocyte/B cell compartment in B cell regulation, we tested B cell responses in 30 ST patients (> 1 year after transplant) and 15 patients with chronic rejection (CR patients). PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture system, and SAC I for T cell- and monocyte-independent B cell stimulation. B cell responses were assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimulated cultures of ST patients, we found a diminished immunoglobulin-secreting cell (ISC) formation (P < 0.0001 and P < 0.05, compared with controls and CR patients, respectively) and diminished IgM secretion (P = 0.06 and P < 0.01, respectively), whereas CR patients and controls were not significantly different. Two of 35 (6%) controls and 3 of 15 (20%) CR patients, in contrast to 20 of 30 (67%) ST patients, displayed defective ISC formation (P < 0.0001). This defective B cell response may be the result of reduced CD36+ monocyte counts in ST patients (P < 0.005), as PWM-stimulated B cell responses and CD36+ cell counts were significantly associated (P < 0.05, ISC and IgM response). A role of monocytes in the impairment of B cell function is further supported by decreased plasma neopterin levels in ST compared with CR patients (P = 0.0001), a significant association between plasma neopterin and PWM-stimulated B cell responses (P < 0.05, ISC response; P = 0.0001, IgM response), and by the finding that B cell responses in ST patients after monocyte-independent stimulation with SAC I were unaffected. ST and CR patients showed no significant differences in B cell subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data indicate that an IL-6-independent monocyte or B cell defect plays a role in the maintenance of stable transplant function.

Thermal injury-associated neopterin production: regulation by interleukin-2.

Pteridin neopterin production by monocytes/macrophages has been linked to the biologic activity of immune activation- and/or infection-related cytokines. In patients with thermal injuries who succumb to infections, serum levels of both interleukin-2 (IL-2) and neopterin are significantly increased. However, the relationship between these two markers of immune activation remains unclear. This study examines the role of IL-2 in the biosynthesis of neopterin after major burn. Up to 4 weeks after burn, the levels of plasma neopterin and endotoxin were elevated in all patients studied (N = 9, 30% to > 90% total body surface area). Intact (unsupplemented) peripheral blood mononuclear cell (PBMC) cultures from patients with sepsis secreted high levels of neopterin spontaneously. The spontaneous release of neopterin was significantly decreased (p < 0.05) after supplementation with exogenous IL-2. The reverse was observed in peripheral blood mononuclear cell cultures from infection-free or control groups where relatively low neopterin secretion was markedly augmented in the presence of IL-2. The effect of IL-2 in patient cultures was unrelated to the activity of endogenous interferon gamma, because the production of this cytokine was profoundly reduced. However, IL-2-induced alterations in neopterin secretion paralleled those in the production of tumor necrosis factor alpha. This suggests that after thermal injury, biologic responses of neopterin-secreting peripheral blood mononuclear cells are directly or indirectly regulated by IL-2.

Free radical activity and loss of plasma antioxidants, vitamin E, and sulfhydryl groups in patients with burns: the 1993 Moyer Award.

This study examines the relationship of burn injury and plasma levels of conjugated dienes, total sulfhydryl groups, and vitamin E in patients with thermal injuries. Plasma neopterin levels were determined as an index of macrophage activity and serine elastase as an index of polymorphonuclear cell activation. Thirteen patients with burns, six survivors and seven nonsurvivors, were studied for the first 4 days, then every other day until postburn day 14. Twelve healthy volunteers served as the control group. Survivors had 56% +/- 4% total body surface area burned, and nonsurvivors had 63.9% +/- % total body surface area burned. The patients with burns, compared with the control group, showed elevated plasma levels of the lipid peroxidation products conjugated dienes (0.767 +/- 0.045 vs 0.269 +/- 0.013 Abs at 233 nm) and reduced levels of the natural scavengers of free radicals, vitamin E (196.2 +/- 12.6 vs 841.1 +/- 22.7 micrograms/dl) and total sulfhydryl groups (54.0 +/- 0.4 vs 15.8 +/- 1.0 mumol/dl). The total sulfhydryl groups/conjugated dienes ratio fell at a greater rate (9.8% +/- 3.2% vs 3.2% +/- 0.7%/day) in nonsurvivors than in survivors (p < 0.05 by Mann-Whitney). The levels of elastase were slightly elevated in the patients with burns, but there was no difference between survivors and nonsurvivors. Normal neopterin levels are 3 to 10 nm/L; peak levels were 119 +/- 48 nm/L in nonsurvivors and 37.4 +/- 10 nm/L in survivors. Patients with burns demonstrated evidence of increased oxygen free radical activity and activation of polymorphonuclear cell and macrophages. Nonsurvivors demonstrated increased consumption of antioxidants compared with survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Neopterin, PMN Elastase, and Complement Components as Monitoring Parameters in Women with the Syndrome of Hemolysis, Elevated Liver Enzymes and Low Platelet Count

SummaryPreeclampsia is a pregnancy induced hypertensive disease with an incidence of about 5% in primigravida and it significantly contributes to maternal and neonatal morbidity and mortality. The primary cause remains unknown but might be immunologic. Our previous studies have shown that complement neutrophils and macrophages are activated in preeclampsia. The present study evaluated whether the extension of the macrophage, the neutrophil and the complement activation is related to the severity of preeclampsia. Patients with severe preeclampsia. complicated by the syndrome of hemolysis. elevated liver enzymes and low platelet count (HELLP) and women with preeclampsia were studied. Women with uncomplicated pregnancies were controls. To detect activation of macrophages and polymorphonuclear neutrophils (PMN), respectively. the formations of neopterin and PMN elastase were analyzed. For evaluation of complement activation. the biologically active components C5a and the terminal C5b-9 complement complex (TCC) were determined in plasma. Patients with the HELLP syndrome had significantly elevated plasma concentrations of neopterin and C5a at delivery compared to women with preeclampsia. and compared to the controls, the HELLP group had significantly raised plasma levels of neopterin. PMN elastase. C5a and TCC. Women with preeclampsia had significantly higher plasma concentrations of neopterin and TeC at delivery as compared to the controls. In preeclamptics and HELLP patients, the plasma concentrations at delivery of PMN elastase, C5a and TCC were normalized within one week. but the plasma levels of neopterin remained elevated after one week. Neopterin, PMN

The influence of hypercholesterolemia on some aspects of immune pattern in the elderly

In order to investigate if age related dislipidemia was associated with immunological changes in vivo, humoral, soluble and cellular immune parameters were evaluated both in elderly with and without hypercholesterolemia and in young adults. Significantly increased IgG and IgA values were found in hypercholesterolemic aged compared to the other groups. Increased plasma neopterin levels (a pteridine generally used as a marker of macrophage activity) were reported in healthy aged subjects, whereas a lesser degree of the activation of the macrophage system was found in the hypercholesterolemic aged subjects. Compared with the young controls, an increase of interleukin 2 receptor expressing cells and of the IL-2 soluble receptors was noticeable in healthy aged subjects, whereas in hypercholesterolemic aged subjects only a minor increase of the IL-2 membrane receptor was noticed. We suggest that hypercholesterolemia may play a role in immune function in aging.

Neopterin plasma levels in burn patients

Burn victims have severely depressed cellular immunity and despite careful hygiene, antibiotics and early surgical therapy the infection rate remains high. The assessment of plasma neopterin levels can be considered as an indirect measurement of macrophage function, because activation of macrophages is accompanied by the release of d-erythro-neopterin. The influence of burn trauma on neopterin levels was investigated to determine whether neopterin estimations might have a prognostic or diagnostic value. Twenty patients with a mean age of 36 ± 16 years and a TBSA of 45.5 per cent ± 23 were studied. During the whole hospital treatment daily blood samples were analysed for neopterin levels using radioimmunoassay. Starting from normal levels (9 ± 1.6 nmol/l), neopterin content increased continuously until day 10 (30–40 nmol/l), then fluctuated around these high levels for several weeks. There were no differences between patients with TBSA < 35 per cent or > 35 per cent, and between survivors and non-survivors. Burn injury caused a constant increase of plasma neopterin indicating an intact reaction by macrophages. It can be used as an additional parameter for the diagnosis of sepsis: high values being a sign of adequate reaction by macrophages, whereas low neopterin values in the presence of bacteraemia and clinical symptoms of sepsis show a deleterious impairment of immune functions.

Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running

This study was designed to examine cytokine production in a group of 22 well-trained runners covering a distance of 20 km within 2 hr. After running, all participants displayed a marked granulocytosis for 7 hr. Plasma neopterin levels increased 1 hr after exercise for 24 hr. Except for interleukin-6 (IL-6), cytokines were not reliably detected in plasma but were present in urine. Already before exercise, cytokines were detected in the urine of runners when compared to sedentary controls. Directly after running, interferon-γ and tumor necrosis factor-α were further elevated but rapidly declined to preexercise levels. Interleukin-1β and interleukin-6 increased at a slower rate after exercise but secretion into urine persisted longer until 12 and 7 hr, respectively. Interleukin-2 (IL-2) was not detected but soluble IL-2 receptors appeared in the urine directly after running. Enhanced cytokine levels were accompanied by an only low creatinin kinase increase, indicating little muscle damage. These data show that long-distance running elevates cytokine production which supports the concept that regular, but not excessive, physical exercise may be beneficial by maintaining a stimulated immune system.

The neonatal immune response to washed and irradiated red cells: lack of evidence of lymphocyte activation

A total of 21 neonatal infants (11 males and 10 females) were evaluated for lymphocyte subpopulation changes and cellular activation following the receipt of washed and gamma-irradiated red cells. The mean donor exposure was 2 +/- 1.5 donors, and the mean white cell concentration of each 10-mL-per-kg transfusion was 2 x 10(7) cells. A total of 2800 rad (28 Gy) was delivered to each red cell unit prior to washing. The lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3+/CD25+, CD3+/HLA-DR, CD4+/CD45RA, CD4+/CDw29, and CD4+/ICHL-1 were analyzed, as were plasma gamma-interferon and neopterin levels, before and after blood transfusion. Posttransfusion samples were obtained from 3 to 12 days after the last blood transfusion. There were no posttransfusion changes in the percentage of lymphocyte subsets analyzed. Furthermore, overlay-histogram analysis of pretransfusion and posttransfusion CD45RA-, CDw29-, and UCHL-1-positive helper T cells failed to reveal a shift in mean channel fluorescence intensity, which is indicative of a lack of cellular activation. Gamma-interferon levels remained unchanged after transfusion (range, 90 +/- 5.9 to 95.5 +/- 5.3 pg/mL), as did neopterin levels (range, 3.7 +/- 1.5 to 4.6 +/- 1.5 ng/mL). This study could not find any evidence, by either cellular or humoral markers, of the activation of neonatal lymphocytes by transfusion. It is hypothesized that this failure to observe lymphocyte activation is due to the low number of donor white cells present in washed, irradiated red cells and/or to a lack of recipient recognition of transfused, allogeneic, donor white cells.

Elevated serum neopterin levels in atherosclerosis

Plasma levels of neopterin were determined in patients with different clinical stages of atherosclerosis. Non-hospitalized patients with atherosclerosis had serum and plasma neopterin levels within the normal range of the assay (6 ± 2 nM). These values were not significantly different from those reported for healthy blood donors (5 ± 2 nM). In contrast, about 50% (29 out of 61) of hospitalized patients undergoing conservative or surgical therapy had neopterin plasma levels, which exceeded the normal range (> 10 nM) up to 10-fold. The two groups differ on a significance level of P < 0.01. For further evaluation hospitalized patients were subgrouped according to neopterin levels. In the subgroup with elevated neopterin levels patients with higher Frederickson types of atherosclerosis were overrepresented compared to patients with normal neopterin levels. Type 4 differed significantly from patients without pathological changes of lipoprotein ( P < 0.05). Only 3 patients suffered from minimal skin necrosis, two of them had elevated neopterin levels. Significantly more patients with peripheral artery occlusions had elevated neopterin levels than patients with occlusions of central arteries ( P < 0.05). All other criteria used for comparison (sex, age, smoking, antioxidant status, diabetes, hypertension, adipositas, hyperuricemia) did not vary significantly in both subgroups. These data indicate that neopterin plasma levels might be a valuable parameter in activity staging and therapeutic follow up of atherosclerosic patients. Additionally, an involvement of the nonspecific immune system in atherogenesis is suggested by the increased plasma neopterin concentrations.

Plasma Neutrophil-Activating Peptide-1/lnterleukin-8 and Neutrophil Elastase in a Primate Bacteremia Model

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.

Immune Activation during Measles: Interferon- and Neopterin in Plasma and Cerebrospinal Fluid in Complicated and Uncomplicated Disease

To study T cell and macrophage activity during measles, levels of interferon-gamma (IFN-gamma) and neopterin in plasma and cerebrospinal fluid (CSF) were measured. Plasma levels of IFN-gamma were elevated in measles (1.17 +/- 0.27) compared with healthy adults (0.13 +/- 0.06, P less than .05) and children (0.14 +/- 0.06, P less than .01). Plasma levels of neopterin were elevated in measles (32.5 +/- 2.7) compared with healthy adults (5.3 +/- 2.9, P less than .0001), healthy children (12.1 +/- 4.0, P less than .001), and children with other infectious diseases (20.6 +/- 4.0, P less than .02). IFN-gamma was increased in measles primarily during rash; neopterin remained elevated for several weeks. Levels of neopterin showed a significant positive correlation with plasma levels of soluble interleukin-2 receptor and soluble CD8, two other parameters of T cell activation. Children with measles complicated by pneumonia had higher levels of neopterin in serum than those with uncomplicated disease. Children with measles complicated by autoimmune encephalomyelitis had higher levels of neopterin in CSF than those with noninflammatory neurologic disease but lower than those with central nervous system infections. Thus, IFN-gamma seems to be produced in vivo during acute measles virus infection; deficiency of this lymphokine does not appear to correlate with increased susceptibility to secondary infections.