Differences in vitamin D nutritional status between newly diagnosed cancer patients from rural or urban settings in Kentucky.

Although poor nutritional status and weight loss in cancer patients is known to affect outcomes, little is known about malnutrition differences based on geographic location. We investigated nutritional and inflammatory status of 220 newly diagnosed adults with solid tumors at the University of Kentucky's Markey Cancer Center during December 2008 through October 2011. Chi-square tests were used to determine any associations between suboptimal nutritional levels and rural-urban areas of residence. Out of the 13 lab values collected, the only significant difference between rural and urban participants was found for vitamin D resulting in more rural subjects (67.4%) having a suboptimal vitamin D status as compared to those residing in urban areas (53.3%, P = 0.04). Controlling for baseline demographics including age, race, sex, body mass index, nutritional status, and type of cancer, logistic regression analyses concluded those in rural areas had nearly a twofold increase in the odds of having a suboptimal vitamin D level compared to those in urban areas (odd's ratio = 1.97; 95% confidence interval = 1.04, 3.74). Further investigation into the rural-urban differences in vitamin D needs to be investigated in order to improve outcomes during cancer treatment.

Inhibition of human erythroid colony-forming units by tumor necrosis factor requires beta interferon.

We have previously reported that inhibition of human CFU-erythroid (E) colony formation by tumor necrosis factor (TNF) is an indirect effect mediated by a soluble factor released from a fraction of marrow accessory cells which are predominantly stromal elements (Means, R. T., Jr., E. N. Dessypris, and S. B. Krantz. 1990. J. Clin. Invest. 86:538-541). Further studies reported here identify a mediator of this effect. The inhibitory effect of recombinant TNF on marrow CFU-E is ablated by neutralizing antibodies to human beta IFN, but not by antibodies to gamma IFN or IL-1. Anti-beta IFN also neutralizes the inhibitory effect of conditioned medium prepared from marrow cells exposed to TNF. Human beta IFN inhibits colony formation by unpurified marrow CFU-E as well as highly purified CFU-E generated from peripheral blood progenitors, and limiting dilution analysis shows that this is a direct inhibitory effect. TNF has been implicated in the pathogenesis of the anemia of chronic diseases since blood TNF levels are elevated in many patients with this syndrome, and since exposure to TNF produces a similar anemia in either humans or mice. The present study demonstrates that beta IFN is a required mediator of this inhibitory effect on erythropoiesis.

Inhibition of human colony-forming-unit erythroid by tumor necrosis factor requires accessory cells.

Recombinant tumor necrosis factor (rTNF) inhibits erythropoiesis in vivo and in vitro. To study the mechanism of this inhibition, the effect of rTNF on highly purified human CFU-erythroid (E) (mean purity 63.5%), which were generated from peripheral blood burst-forming units-erythroid (BFU-E), was compared to its effect on unpurified human marrow CFU-E (mean purity 0.21%). Although growth of colonies from marrow CFU-E was inhibited by rTNF, no significant effect on purified BFU-E-derived CFU-E colony growth was found. Removal of accessory marrow cells by soy bean agglutinin (SBA) ablated the inhibition of marrow CFU-E colonies by rTNF. Inhibition of colony growth was then restored by adding back SBA+ cells, but not by adding T lymphocytes or adherent cells. Conditioned medium prepared from bone marrow mononuclear cells stimulated by rTNF inhibited the growth of colonies from highly purified BFU-E derived CFU-E resistant to direct inhibition by rTNF. These findings indicate that rTNF does not directly inhibit CFU-E, but requires accessory cells to decrease erythropoiesis. These accessory cells reside in the SBA+ cell fraction, but are neither T cells nor adherent cells. Therefore, in order to produce anemia, TNF must induce release or production of a factor that directly inhibits erythroid colony growth.

Erythropoietin receptors in polycythemia vera.

The role of erythropoietin (EP) in polycythemia vera (PV) is controversial, with some experiments suggesting that erythroid progenitors in PV are exquisitely sensitive to EP and EP dependent, and others suggesting that PV progenitors are EP independent. We have examined the characteristics of the EP receptor (EP-R) on erythroid colony-forming cells (ECFC) from patients with PV. In contrast to normal ECFC, which have two classes of EP-R, with 20% showing high affinity (Kd = 0.13 nM; range, 0.04-0.20 nM) and the remainder lower affinity (Kd = 0.37 nM; range, 0.28-0.57 nM), PV ECFC show a single class of 851 low affinity EP-R with Kd = 0.72 nM (range, 0.36-0.85 nM). ECFC from patients with secondary (EP driven) polycythemia or anemia show two classes of EP-R (Kd = 0.18 and 1.10 nM, respectively). Attempts to remove tightly bound EP from putative high affinity EP-R in PV did not reveal any higher affinity receptors. Determination of molecular size by crosslinking showed two proteins of 90 and 100 kD similar to those seen with normal EP-R. These studies indicate the PV ECFC have EP-R that are structurally similar to normal EP-R but lack the higher binding affinity for EP.

Polycythemia vera blood burst-forming units-erythroid are hypersensitive to interleukin-3.

Because polycythemia vera (PV) is a clonal hematopoietic stem cell disease with a trilineage hyperplasia, and interleukin-3 (IL-3) stimulates trilineage hematopoiesis, we have studied the response of highly purified PV blood burst-forming units-erythroid (BFU-E) to recombinant human IL-3 (rIL-3). Whereas the growth of normal blood BFU-E in vitro rapidly declined by 40 and 60% after 24 and 48 h of incubation without 50 U/ml of rIL-3, the growth of PV BFU-E declined by only 10 and 30% under the same conditions, demonstrating a reduced dependence on rIL-3. A reduced dependence of PV BFU-E on recombinant human erythropoietin (rEP) was also present. Dose-response experiments showed a 117-fold increase in PV BFU-E sensitivity to rIL-3, and a 6.5-fold increase in sensitivity to rEP, compared to normal BFU-E, whereas blood BFU-E from patients with secondary polycythemia responded like normal BFU-E. Endogenous erythroid colony (EEC) formation, which is independent of the addition of rEP, was reduced by 50% after erythroid colony-forming cells were generated from PV BFU-E in vitro without rIL-3 for 3 d, whereas rEP-stimulated erythroid colonies were unaffected. These studies demonstrate a striking hypersensitivity of PV blood BFU-E to rIL-3, which may be the major factor in the pathogenesis of increased erythropoiesis without increased EP concentrations.

Expression of receptor protein tyrosine kinase tif is regulated during leukemia cell differentiation.

tif is a recently cloned and characterized cDNA predicting a transmembrane protein with a putative tyrosine kinase structure in its cytoplasmic domain. By analysis of the purified tif cytoplasmic domain expressed in Escherichia coli, we have demonstrated that tif is an active protein tyrosine kinase capable of autophosphorylation on tyrosine residues and this phosphorylation is inhibited by a tyrosine-specific inhibitor genistein. Northern blot analyses of various leukemia cell lines have revealed that tif mRNA expression is primarily confined to those bearing erythroid and megakaryocytic phenotypes. Megakaryocytic differentiation of K562 and HEL cells induced by phorbol 12-myristate 13-acetate is accompanied by down-regulation of tif mRNA expression. In addition, treatment of K562 and HEL with hexamethylene bis-acetamide, but not with hemin, decreases the steady-state level of tif mRNA. These combined results suggest that the receptor tyrosine kinase tif is involved in hematopoietic development.

Inhibition of human erythroid colony-forming units by interferons alpha and beta: differing mechanisms despite shared receptor.

Previous investigations have demonstrated that interferons alpha, beta, and gamma (alpha-, beta-, and gamma-IFN) are potent inhibitors of erythropoiesis in vitro. By utilizing a cell population enriched for human erythroid colony-forming units (CFU-E), we have previously demonstrated that the inhibitory effects of beta- and gamma-IFNs are direct effects, not requiring the presence of accessory cells, and that the inhibitory effect of recombinant human (rh) gamma-IFN could be corrected by high concentrations of rh erythropoietin (Epo). In this study, we compared the effects of rh(alpha)-IFN on cells enriched for CFU-E to its effects on unpurified marrow cells and found that although h(beta)-IFN (which shares a common receptor with alpha-IFN) directly inhibits CFU-E colony formation, the effect of rh(alpha)-IFN is indirect and is mediated by a soluble factor released from T lymphocytes in response to rh(alpha)-IFN. However, rh(alpha)-IFN enhanced the direct inhibitory effect of rh(gamma)-IFN on CFU-E not inhibited by rh(alpha)-IFN. The inhibitory effects of neither alpha- nor beta-IFN could be overcome by high levels of rhEpo. These findings imply that alpha- and beta-IFN exert different cellular effects despite binding to the same receptor. Failure of rhEpo to correct CFU-E colony inhibition by alpha- and beta-IFNs but not by gamma-IFN also suggests a mechanism for the differing degrees of response to different doses of rhEpo in patients with the anemia of chronic disease.

Inhibition of human erythroid colony formation by ceramide.

In previous studies, we have demonstrated that the inhibitory effects of tumor necrosis factor (TNF) and interleukin (IL)-1 on human erythroid colony formation are indirect and mediated by beta and gamma interferon (IFN), respectively, which act directly upon erythroid colony forming units (CFU-E). The in vitro inhibitory effect of gammaIFN but not betaIFN is reversed by exposure to high concentrations of recombinant human (rh) erythropoietin (EPO). Ceramide, a product of sphingomyelin hydrolysis, is a known mediator of apoptotic effects of TNF, IL-1, and gammaIFN. In this report, the effects of ceramide on CFU-E colony formation and its implication in the model described above are evaluated. Endogenous ceramide produced by exposure to bacterial sphingomyelinase (0.2-2.0 U/mL) and exogenous cell-permeable ceramide (C2-ceramide; 5 and 10 mM) significantly inhibited bone marrow CFU-E colony formation. This effect was reversed by the ceramide antagonist sphingosine-1-phosphate (S-1-P). Inhibition of CFU-E by rhgammaIFN, but not rhbetaIFN, was significantly reversed by S-1-P. rhEPO 10 U/mL reversed CFU-E inhibition by C2-ceramide 10 mM. Exposure of marrow cells to rhgammaIFN led to a 57% increase in ceramide content. The present study demonstrates that colony formation by human CFU-E is inhibited by endogenous and exogenous ceramide, and that inhibition by rhgammaIFN can be reversed by the ceramide antagonist S-1-P. Inhibition of CFU-E colony formation by ceramide and by are both reversed by high concentrations of rhEPO. These findings strongly suggest that ceramide mediates inhibition of human CFU-E colony formation by gammaIFN.

Quantitation of insulin-like growth factor-I binding to highly purified human erythroid colony-forming units.

A method has been developed by which erythroid colony-forming units (CFU-E) may be obtained from human blood in sufficient number and purity for quantitative studies of growth factor binding. Studies in serum-free medium have shown that CFU-E require the addition of only two growth factors, erythropoietin (EP) and insulin-like growth factor-I (IGF-I), for growth and differentiation. The IGF-I may be replaced by higher (100-fold) concentrations of insulin. Incubation of CFU-E with 125I recombinant human IGF-I (rhIGF-I) at 4 degrees C has demonstrated specific binding that is directly proportional to the cell concentration. Competition with unlabeled rhIGF-I markedly decreased binding, whereas other growth factors such as granulocyte-monocyte colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and epidermal growth factor (EGF) had no significant effect on the binding of [125I]rhIGF-I. The binding was saturable at an [125I]rhIGF-I concentration of 10 ng/ml (1.2 nM). Scatchard analysis revealed two classes of IGF-I receptors present on the CFU-E cell surface: a low-affinity class of 549 receptors with Kd = 0.44 nM and a high-affinity class of 341 receptors with Kd = 0.04 nM.

Serum chemokine levels in patients with non-progressing HIV infection.

OBJECTIVE: To evaluate serum chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and RANTES, concentrations in non-progressing HIV-infected patients and AIDS patients. SETTING: University Hospital-based AIDS Clinical Trials Unit. DESIGN/METHODS: Serum MIP-1 alpha, MIP-1 beta and RANTES levels were determined by enzyme-linked immunosorbent assay using archived serum specimens obtained on two occasions at least 1.8 years apart. PATIENT SELECTION: Long-term non-progressing HIV-infected adult patients were identified from clinic records. For each non-progressing patient two adult AIDS patients with initial documentation of seropositivity the same year and the same length of follow-up were selected. RESULTS: Four long-term non-progressing patients and eight AIDS patients were studied. Neither the duration of known HIV positivity at the time of specimen collection nor the length of time between specimen collections differed significantly between non-progressing patients and AIDS patients. Serum levels of MIP-1 alpha, MIP-1 beta and RANTES in specimens obtained either early or later in the course of HIV infection did not differ significantly between non-progressing patients and AIDS patients. In the two patient subsets, significant differences in serum chemokine levels over time were not observed. The rate of change of serum chemokine concentration over time also did not differ between non-progressing patients and AIDS patients. Serum MIP-1 alpha and MIP-1 beta levels did not reach levels reported to suppress HIV proliferation in vitro. When expressed as a quantity per peripheral blood CD8+ lymphocyte, AIDS patients exhibited significantly greater levels of MIP-1 alpha, MIP-1 beta and RANTES than non-progressing HIV patients (P < 0.05). These values did not exhibit a significant variation over time. CONCLUSIONS: Serum MIP-1 alpha, MIP-1 beta and RANTES levels do not distinguish patients with AIDS from patients with non-progressing HIV infection. Variations in levels of these chemokines do not explain individual variation in the natural history of HIV infection.

Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance.

PURPOSE: To establish the frequency with which serum ferritin levels > or = 1,000 ng/mL occur in a general hospital population, and to determine the clinical significance of this finding. PATIENTS AND METHODS: All serum ferritin determinations performed between June 1992 and July 1993 at the University of Cincinnati Medical Center were reviewed and patients with serum ferritin levels > or = 1,000 ng/mL identified. The medical records of these patients were then reviewed. RESULTS: Of 1,826 serum ferritin determinations performed during the study period, 122 (6.7%) were > or = 1,000 ng/mL. Associated clinical syndromes found in the 95 patients with serum ferritin > or = 1,000 ng/mL included liver disease (20.0%), renal disease (17.9%), malignant disease (17.9%), human immunodeficiency virus (HIV) infection (16.8%), non-HIV systemic infections (15.8%), chronic transfusions (10.5%), and sickle cell syndromes (10.5%). No syndrome usually associated with extreme serum ferritin elevations was identified in 8.4% of patients, and 16.8% of the patients fell into more than one category. The highest mean serum ferritin levels occurred in the chronically transfused and sickle cell groups. Concomitant serum transferrin saturation values were determined with 82 (86.3%) of the elevated serum ferritin levels and did not correlate well with them. The highest mean transferrin saturation levels occurred in the liver disease group. Transferrin saturation > or = 50%, suggestive of iron overload, was significantly more frequent in the liver disease group (P = 0.002); and saturation < or = 15%, suggestive of iron-deficient erythropoiesis, was significantly more frequent in the HIV group (P = 0.001). CONCLUSION: Outside the setting of clinical syndromes associated with iron overload (liver disease, transfusions, sickle cell syndromes), serum ferritin levels > or = 1,000 ng/mL serve as a nonspecific marker for a variety of significant disorders, including infectious and neoplastic diseases. Further study of the regulation of ferritin production may provide insight into the pathogenesis of disorders associated with extreme serum ferritin elevations.

Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Advances in the anemia of chronic disease.

The anemia found in patients with chronic infectious, inflammatory, and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines that mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin-1, and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin, and abnormal mobilization of reticuloendothelial iron stores. In this review, advances in the understanding of the diagnostic, pathophysiologic, and therapeutic aspects of this syndrome are summarized.

Clinical application of recombinant erythropoietin in the anemia of chronic disease.

The anemia of chronic disease is a consequence of the abnormal production of cytokines associated with chronic inflammatory, infectious, and neoplastic disorders. rhEPO can correct the impaired erythropoiesis encountered with this syndrome in vitro and in the clinical setting. Although most patients with the anemia of chronic disease will not require specific intervention to increase their hemoglobin and hematocrit, certain subsets of patients may benefit from rhEPO therapy. These include patients with anemia sufficiently severe to require transfusion, and patients for whom autologous blood donation is precluded by anemia.

Unanticipated favorable effects of correcting iron deficiency in chronic hemodialysis patients.

BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail. METHODS: Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. RESULTS: With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset. CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores.

Cytokine and cytokine receptor concentrations in bone marrow supernatant from patients with HIV: correlation with hematologic parameters.

BACKGROUND: To determine the concentrations of tumor necrosis factor (TNF) alpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interferon (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES to which hematopoietic progenitors are exposed in vivo in HIV patients and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bone marrow aspirate supernatants from 19 HIV patients undergoing diagnostic evaluation and 14 healthy paid volunteer controls. IL-1 beta and gamma-IFN were rarely detectable. All cytokines/receptors detectable in marrow supernatant, except RANTES, showed mean concentrations 1.6- to 6.2-fold higher in patients with HIV compared to healthy controls. METHODS: Elevated TNF-alpha and MIP-1 beta were associated with marrow involvement by lymphoma, Hodgkin disease, or mycobacterial infection. Concentrations of all cytokines/receptors measured correlated with the severity of anemia. CD8+ lymphocytes were inversely correlated with concentrations of all cytokines measured other than MIP-1 alpha. To identify differences specific to HIV infection, marrow supernatant cytokine concentrations were also evaluated in 9 non-HIV patients undergoing diagnostic marrow examination. Significant differences were observed in TNF alpha, MIP-1 alpha, and IL-1 beta concentrations. RESULTS: These studies demonstrate that concentrations of these cytokines and receptors are elevated in bone marrow supernatant of HIV-infected patients with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients. CONCLUSIONS: Evaluation of local concentrations of cytokines may be relevant to understanding tissue-specific pathology in HIV-infected individuals.

Treatment of aplastic anemia with an investigational antilymphocyte serum prepared in rabbits.

The authors evaluated antilymphocyte serum prepared in rabbits (ALS-R) as an alternative to antilymphocyte serum prepared in horses (ALG-H) in the therapy of aplastic anemia. Between 1980 and 1993, 57 evaluable patients received ALS-R and prednisone +/- cyclosporine +/- androgens. Standard response criteria were used and patients were evaluated at 3 months from the start of therapy. Median age was 43 years. Disease was present for up to 2 months in 24 patients, 2-5 months in 14 patients, and 6 months or more in 19 patients. Disease was severe in 30 patients and moderate in 27. Responses occurred in 16 (28%) of 57 patients. Responses were more frequent in females, in patients treated within 6 months of diagnosis, and in patients with severe disease. Among patients receiving ALS-R and cyclosporine within 2 months of diagnosis, 46% responded. After ALS-R therapy, 20 patients received ALG-H; 8 (40%) of 20 responded. Eight patients receiving ALS-R previously had received ALG-H; 2 (25%) of these 8 patients responded. Toxicity of ALS-R was minimal. Antilymphocyte serum prepared in rabbits, in conjunction with other immunosuppressive agents, represents an effective alternative to ALG-H in aplastic anemia, especially in patients previously treated with ALG-H.

Cytokine response to BCG infection in alcohol-fed mice.

Alcoholics have increased susceptibility to infections including tuberculosis. Chronic alcohol treatment impairs host response to bovine mycobacterium infection from BCG. This study assesses the role of four cytokines (TNFalpha, IFNgamma, IL-4, and IL-10) in this impaired response. Twenty male C57BL/6 mice were pair-fed on the Lieber DiCarli control (LCD) or ethanol (LED) diets for 28 days. The LED treated subjects ate ad lib and consumed a mean of 13 g/kg/d of ethanol. After 14 days, based on body weight, subjects were randomly divided into four treatment groups of five each. Ten infected with 2x10(6) colony-forming units (CFU) of BCG by tail-vein. On day 28, the mice were sacrificed. Liver was cultured to determine the mycobacteria CFU/g tissue. Spleens were assayed for the levels of TNFalpha, IFNgamma, IL-4, and IL-10 mRNA relative to mRNA levels for a housekeeping gene using a quantitative reverse transcriptase PCR. Without BCG infection, only the mRNA for IFNgamma was increased by LED treatment, 51% (p = 0.0001). BCG infection significantly increased TNFalpha, IFNgamma, and IL-10 mRNA (p<0.0001). IL-4 mRNA decreased (p = 0.0006). Chronic LED plus BCG infection further increased TNFalpha (p = 0.002) and IFN-gamma (p = 0.04); IL-10 was unchanged, whereas IL-4 was marginally further decreased (p = 0.06). CFU/liver increased with LED (mean +/- SD, 72+/-33x10(5) vs. 39+/-17x10(5); p = 0.004). A significant direct correlation was observed between CFU and TNFalpha, r = 0.70, p = 0.03. In conclusion, BCG infection increases TNFalpha, IFNgamma, & IL-10 and decreases IL-4. CFU numbers correlate with mRNA for TNFalpha, and LED inhibits host containment of BCG infection as measured by liver CFU. This study could not identify cytokine alterations in either Th1- or Th2-type immune responses that might contribute to the impaired host response to the BCG infection.