Biomedical subjects

C S Hirsch

Publications and source records attributed to C S Hirsch.

At least 37 records · Page 2Linked to original sources

PubMed1997

In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta.

We examined the capacity of the naturally occurring inhibitors of transforming growth factor beta (TGF-beta), decorin and latency associated peptide (LAP), to reverse depressed T cell functions in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (TB) in vitro and to counteract the suppressive properties of TGF-beta on mycobacterial replication in blood monocytes (MN) in vitro. T cell blastogenesis in response to purified protein derivative (PPD) in PBMCs of TB patients that were cocultured with decorin or LAP reached levels comparable to those observed in healthy tuberculin-responsive control subjects. Decorin and LAP were as effective as neutralizing antibody to TGF-beta in correcting depressed T cell proliferation. Coculture of PBMCs from healthy PPD reactive individuals with neutralizing antibody to TGF-beta, decorin, or LAP did not affect T cell blastogenesis. Levels of interferon-gamma in cultures of PPD-stimulated PBMCs from patients with TB increased by more than 2-fold in the presence of maximal concentrations of either of the inhibitors of TGF-beta, whereas TGF-beta immunoreactivity declined to background levels. Coculture with optimal concentrations of decorin or LAP also led to reductions in mycobacterial growth in MN infected with Mycobacterium tuberculosis (MTB) in vitro by 51% and 62%, respectively, when compared with cells left untreated. In parallel, levels of immunoreactive TGF-beta in MTB-infected MN cultures containing decorin or LAP decreased to background levels. These data indicate that the naturally occurring inhibitors of TGF-beta, decorin and LAP, efficiently abrogate the suppressive effects of TGF-beta in PBMCs of TB patients and in MN infected with MTB in vitro. Therefore, these agents may be considered as adjuncts to antituberculous chemotherapy, and may be particularly useful in treatment of TB that is unresponsive to conventional chemotherapy.

Cell Division↗

PubMed1997

Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression/anergy.

Protective immunity against Mycobacterium tuberculosis (MTB) in animal models is based on cell-mediated immunity (CMI), involving bi-directional interactions between T cells and cells of the monocyte/macrophage (MO/MA) lineage. Key factors include MO-derived interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha as well as T cell derived IL-2 and interferon (IFN)-gamma. These cytokines appear particularly crucial in the induction of MA-mediated elimination of mycobacteria. Several lines of evidence indicate that similar mechanisms are operating in humans. During active pulmonary tuberculosis (PTB), signs of both immune depression and immune activation are concomitantly present. Decreased tuberculin skin test reactivity in vivo and deficient IFN-gamma production by MTB-stimulated mononuclear cells in vitro are observed. On the other hand, the serum levels of several cytokines, including TNF, and other inflammatory mediators are increased and circulating MO and T cell show phenotypic and functional evidence of in vivo activation. In this review, we will discuss the evidence for three models, which could explain this apparent paradox: 1. Stimulation of the T cell-suppressive function from MO/MA; 2. Intrinsic T cell refractoriness, possibly associated with tendency to apoptosis (programmed cell death), and 3. Compartmentalization and redistribution of immune responses to the site of disease. The opportunistic behavior of MTB during human immunodeficiency virus (HIV) infection can be explained by suppression of type-1 responses at the level of antigen-presenting cells, CD4 T cells and effector macrophages. The ominous prognostic significance of intercurrent PTB during HIV infection seems primarily due to prolonged activation of HIV replication in macrophages. Supportive immune therapy during PTB could aim at correcting the type-1 deficiency either by IFN-gamma inducers (e.g. IL-12, IL-18) or by neutralizing the suppressive cytokines transforming growth factor beta (TGF-beta) and IL-10. Alternatively, inflammatory over-activity could be reduced by neutralizing TNF. Finally, anti-apoptotic therapies (e.g. IL-15) might be considered.

Cytokines↗

PubMed1997

Lower risk of suicide during pregnancy.

OBJECTIVE: The authors determined the risk of suicide during pregnancy. METHOD: The autopsy reports of all female residents of New York City, 10-44 years old, who committed suicide from 1990 to 1993 were assessed for pregnancy. These data were compared with age-adjusted and race-adjusted standardized mortality ratios for women, which were calculated by using population data from the 1990 U.S. Census as well as data obtained from the New York City Health Department on the number of live births, spontaneous abortions, and induced abortions. RESULTS: The standardized mortality ratio for suicide during pregnancy was 0.33; that is, the number of suicides of pregnant women was only one-third of that expected. CONCLUSIONS: Despite the mood swings and stresses associated with pregnancy and impending childbirth, pregnant women have a significantly lower risk of suicide than women of childbearing age who are not pregnant.

Adult↗

PubMed1997

HIV seroprevalence among suicide victims in New York City, 1991-1993.

OBJECTIVE: The authors sought to determine the HIV seroprevalence among suicide victims in New York City. METHOD: All suicides of city residents from 1991 through 1993 were studied. The crude proportion of all suicide victims who were HIV positive and the proportion adjusted to the age, gender, and racial/ethnic characteristics of the New York City population were determined. The demographically adjusted proportion was then contrasted with HIV seroprevalence estimates for the New York City general population. HIV-seropositive suicide victims were assessed for pathological findings suggestive of HIV-related illnesses. RESULTS: The crude proportion of all suicide victims who were HIV seropositive was 0.088, and the demographically adjusted proportion was 0.049. Over 90% of all HIV-positive suicide victims were aged 25 to 54 years, and almost 90% were men. Among black and Hispanic men aged 35 to 54 years who committed suicide, the proportion who were HIV seropositive was 0.252--the highest seropositive rate of any demographic group. More than two-thirds of HIV-seropositive suicide victims had no HIV-related pathology or AIDS-indicator conditions at autopsy. CONCLUSIONS: The demographically adjusted proportion of suicide victims who were HIV positive (approximately 0.038 to 0.059), contrasted with the HIV seroprevalence estimates for the New York City general population (approximately 0.014 to 0.032), the absence of HIV-related pathology among suicide victims, and the likelihood that many HIV-positive individuals had other risk factors for suicide, such as substance abuse, suggests that a positive HIV serostatus is associated, at most, with a modest elevation in suicide risk.

Adult↗

PubMed1997

Poverty and fatal accidental drug overdoses of cocaine and opiates in New York City: an ecological study.

This ecological study examines the association of the poverty status of urban communities in New York City with their mortality rates of accidental drug overdoses. Mean annual age-adjusted rates of drug overdoses involving cocaine, opiates, or both (n = 1,684) were calculated for each of 59 residential community districts in New York City for 1990-1992. A linear regression analysis was performed to test the association of the mortality rate with the poverty status of the district as measured by the proportion of the district living below the 1989 U.S. poverty line. Poverty status accounted for 69% of the variance in the drug overdose mortality rates of communities (p < .001). This study suggests that mortality rates of overdoses involving cocaine and optiates are significantly associated with the poverty status of communities in New York City.

Adolescent↗

PubMed1997

HIV infection among victims of accidental fatal drug overdoses in New York City.

AIMS: To determine the factors associated with HIV seroprevalence rates for victims of drug overdoses. DESIGN: Descriptive epidemiologic survey of a complete 3-year sample of accidental fatal drug overdoses. SETTING: New York City (population 7,322,564). PARTICIPANTS: All people over 15 years of age (n = 2159) who died of accidental fatal drug overdoses during 1991-93. MEASUREMENTS: Using medical examiner data and logistic regression analyses were conducted to examine the association between HIV seroprevalence and gender, race, age and type of drug overdose. FINDINGS: There were 646 (29.9%) victims who were HIV positive. Women (37.5%) were more likely than men (27.9%) to be HIV positive. African-Americans (39.4%) had a higher rate of HIV infection than Latinos (27.5%), whites (19.2%) or Asians (8.3%). Victims residing in communities with higher levels of poverty had higher rates of HIV infection but poverty did not account for the high rates of HIV infection among African-Americans. The highest rates of HIV infection were found among victims aged 35-44 years (38.8%) and 45-54 years (33.7%). Dying from an opiate overdose was associated with a 2.4 times increase in the likelihood of being HIV positive. CONCLUSION: If opiate abuse continues to rise in the United States, HIV infection will increase in the next few years. Women who abuse drugs participate in risky sexual practices and are more likely than men to develop HIV infection from receptive sex as well as sharing of needles. Harm reduction programs should address risky sex as well as needle programs. There should be further study of why African-Americans who died of drug overdoses have the highest rates of HIV infection.

Adolescent↗

PubMed1997

HIV seroprevalence rates among homicide victims in New York City: 1991-1993.

This study assessed HIV seroprevalence in homicide victims killed in New York City in 1991-1993, using data from the Office of Chief Medical Examiner. Among 5852 homicide victims there were 344 (5.9%) victims who were HIV positive. Females were just as likely as males to be HIV positive. For females, the highest rates were in the 25-34 year (11.7%) and 35-44 year (12.6%) age categories. For males the highest rates were in the 35-44 year (13.7%) and 45-54 year (11.5%) age categories. Other than there being no HIV positive Asian victims, there were no differences in HIV rates among racial/ethnic groups. The highest rates of HIV infection for homicide victims were among those using both opiates and cocaine (males: 23.0%; females: 27.3%). Women, not men, using cocaine alone had a high HIV positive rate (18.4%). Victims not using these drugs had rates of HIV around 2%. The authors believe that the high risk of HIV among homicide victims, may be due to the use of cocaine and associated risky use of needles and risky sex practices.

Adolescent↗

PubMed1997

Modulation of IL-12 by transforming growth factor-beta (TGF-beta) in Mycobacterium tuberculosis-infected mononuclear phagocytes and in patients with active tuberculosis.

In humans, tuberculosis is associated with suppression of T-cell responses to antigens of Mycobacterium tuberculosis. Recently, the macrophage product, transforming growth factor-beta (TGF-beta) has been implicated in suppression of T-cell proliferation and cytokine production during tuberculosis. We studied the effect of TGF-beta on production of IL-12, and on the augmentation of M. tuberculosis-induced IFN gamma production by IL-12, in patients with pulmonary tuberculosis and by M. tuberculosis. Induction of IL-12 p35, but not IL-12 p40, by M. tuberculosis in monocytes was dependent on prior priming of the cells with IFN gamma. Expression of both IL-12 p40 and p35, however, was suppressed by TGF-beta. Further, TGF-beta interfered with the bioactivity of IL-12 in the enhancement of M. tuberculosis-induced IFN gamma mRNA expression and cytokine production. However, in mononuclear cells from patients with tuberculosis the main effect of TGF-beta on IL-12 appeared to be counter action to IL-12 induced IFN gamma production in response to M. tuberculosis.

Gene Expression Regulation↗

PubMed1996

Decreased production of TGF-beta 1 by human alveolar macrophages compared with blood monocytes.

As the main immunocytes lining pulmonary alveoli, alveolar macrophages (AM) are critical to the maintenance of immune hemostasis of the lung. This study examined the capacity of AM obtained from healthy individuals in comparison with autologous blood monocytes (MN) to produce transforming growth factor-beta 1 (TGF-beta), a pivotal molecule in regulation of immune responses and in promotion of fibrosis. AM produced negligible TGF-beta in response to LPS at both 24 and 72 h of culture. In contrast, LPS induced significant levels of TGF-beta in MN cultures (79.5 +/- 35 pg/ml in AM vs 890 +/- 162 pg/ml in MN, p less than 0.001, at 24 h). AM also produced significantly less TGF-beta than MN in response to phorbol ester and Con A. By northern blot analysis, constitutive expression of TGF-beta mRNA was lower in AM than MN at the time of isolation and after 24 h of culture. Lower expression of steady state TGF-beta message was not due to a more rapid decay of its mRNA in AM. Furthermore, TGF-beta mRNA expression was up-regulated by rTGF-beta in MN but was not induced in AM. In contrast to TGF-beta, LPS-stimulated AM produced sixfold higher levels of TGF-alpha at 24 h than MN (p less than 0.01). Production of IL-10 by LPS-stimulated AM was sixfold lower than MN (p less than 0.005) at 24 h of culture, but was comparable with MN at 72 h. Both 10-day cultured monocytes and peritoneal macrophages also had reduced capacity to produce TGF-beta. Therefore, the inability to produce TGF-beta may be a feature of more differentiated mononuclear phagocytes. In health, the reduced expression of TGF-beta by AM and the intact ability to produce TGF-alpha and IL-10 may favor a timely and regulated host response to inhaled pathogens while limiting potentially deleterious inflammatory responses.

Cells, Cultured↗

PubMed1996

Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production.

In tuberculosis, Mycobacterium tuberculosis (MTB)-stimulated T-cell responses are depressed transiently, whereas antibody levels are increased. Lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) from Pakistani tuberculosis (TB) patients to both mycobacterial and candidal antigens were suppressed by approximately 50% when compared to healthy purified protein derivative (PPD)-positive household contacts. Production of interferon gamma (IFN-gamma) in response to PPD also was depressed by 78%. Stimulation with PPD and the 30-kDa alpha antigen of MTB (30-kDa antigen) induced greater secretion of transforming growth factor beta (TGF-beta), but not interleukin 10 (IL-10) or tumor necrosis factor alpha (TNF-alpha), by PBMCs from TB patients compared to healthy contacts. The degree of suppression correlated with the duration of treatment; patients treated for <1 month had significantly lower T-cell blastogenesis and IFN-gamma production and higher levels of TGF-beta than did patients treated for >1 month. Neutralizing antibody to TGF-beta normalized lymphocyte proliferation in response to PPD, partially restored blastogenesis to candidal antigen, and significantly increased PPD-stimulated production of IFN-gamma in TB patients but not in contacts. Neutralizing antibody to IL-10 augmented, but did not normalize, T-cell responses to both PPD and candida in TB patients and candidal antigen in contacts. TGF-beta, produced in response to MTB antigens, therefore plays a prominent role in down-regulating potentially protective host effector mechanisms and looms as an important mediator of immunosuppression in TB.

Antigens, Bacterial↗

PubMed1996

Neuropathology of human immunodeficiency virus infection at different disease stages.

The authors studied the brains of 471 adults infected with human immunodeficiency virus type 1 (HIV-1): 123 asymptomatic carriers, 127 in an early stage of acquired immunodeficiency syndrome (AIDS) with pulmonary tuberculosis or bacterial infections, and 221 in fully developed AIDS with opportunistic infections or neoplasms. Lymphocyte infiltration of the leptomeninges and of perivascular spaces occurred at all stages, but the frequency was significantly higher in asymptomatic carriers. Microglial nodules appeared at all stages of disease; they were not an early indicator of HIV encephalitis (HIVE). The incidence of HIVE was unrelated to the stage of AIDS, suggesting that HIVE occurs before opportunistic infections and neoplasms. Drug abuse, such as cocaine and opiates, may enhance HIV replication and increase the incidence of HIVE in the early stage of AIDS. Opportunistic infections or lymphoma involved only the brain in 31.2% of persons with fully developed AIDS. Conversely, opportunistic infections or neoplasms involved only organs other than the brain in 55.7% of persons with fully developed AIDS. In 13.1% of persons with fully developed AIDS, opportunistic infections or neoplasms involved the brain and other organs. Multiple intracranial opportunistic infections and lymphoma coexisted in 4.1% of persons with fully developed AIDS. The authors identified cerebrovascular disease in 10.6% of asymptomatic carriers, 7.1% of early AIDS, and 5.0% of fully developed AIDS. The observed sequence of abnormalities may be useful in understanding the progression of HIV disease in the brain.

AIDS Dementia Complex↗

PubMed1996

Accidental fatal drug overdoses in New York City: 1990-1992.

This study of all accidental fatal drug overdoses (N = 1,986) in New York City from 1990 to 1992, using medical examiner data, found that cocaine, often with opiates and ethanol, caused almost three-fourths of deaths, while opiates without cocaine caused roughly one-fourth of fatal overdoses. Only 5% of accidental drug fatalities were caused by drugs other than cocaine or opiates. This is a marked departure from the results of studies in the early 1980s when opiates prevailed as a cause of accidental fatal overdoses. In this study the highest cocaine overdose rates were found among males, African-Americans, and Latinos. Rates of opiate overdose without cocaine did not differ in regard to race/ethnicity except for low rates among Asians and other ethnic groups. There was a marked increase in the rate of combined cocaine and opiate overdoses from 1990 to 1992 and a more gradual but steady increase of overdoses due to opiates without cocaine during that time period. Overdoses due to drugs other than cocaine or opiates showed no increase during that time period.

Accidents↗

PubMed1995

Fatal injuries after cocaine use as a leading cause of death among young adults in New York City.

BACKGROUND: Cocaine intoxication can lead to fatal cardiovascular and cerebrovascular events. In addition, the neurobehavioral effects of cocaine may increase the likelihood that a user will receive violent fatal injuries. Since New York City is a center for the importation and distribution of cocaine, we sought to determine the extent of cocaine use among city residents with fatal injuries. METHODS: Among a total of 14,843 residents of New York City who received fatal injuries from 1990 through 1992, we determined the proportion who used cocaine shortly before their deaths. We also determined the population-based rates of fatal injuries that were known to follow cocaine use and the proportion of all deaths of New York City residents that was represented by these cases for each demographic stratum. For adults 15 to 44 years of age, fatal injury after cocaine use was ranked with other causes of death as though it was a separate cause. RESULTS: Cocaine use, as measured by the detection of the metabolite benzoylecgonine in urine or blood, was found in 26.7 percent of all New York City residents receiving fatal injuries; free cocaine was detected in 18.3 percent. Approximately one third of deaths after cocaine use were the result of drug intoxication, but two thirds involved traumatic injuries resulting from homicides, suicides, traffic accidents, and falls. If fatal injury after cocaine use was considered as a separate cause of death, it would rank among the five leading causes of death among those 15 to 44 years of age in New York City. CONCLUSIONS: Fatal injuries among cocaine users account for a substantial proportion of all deaths among young adults in New York City.

Adolescent↗

PubMed1995

Cocaine induced intracerebral hemorrhage: analysis of predisposing factors and mechanisms causing hemorrhagic strokes.

We analyzed 26 autopsy cases of cocaine induced intracerebral hemorrhage and compared those findings with those of 26 autopsy cases of cocaine induced cerebral aneurysm rupture. The incidence of hypertensive cardiovascular disease (HCVD) was significantly higher in persons with intracerebral hemorrhage than in those with aneurysm rupture. Our findings suggest that HCVD predisposes to cocaine induced intracerebral hemorrhage. We propose that the foregoing relationship results from a cocaine induced alteration of cerebral autoregulation in the context of increased cerebral blood flow.

Adult↗

PubMed1995

Use of prescription psychotropic drugs among suicide victims in New York City.

OBJECTIVE: The authors examined the rate of prescription psychotropic drug use among suicide victims at the time of their death. METHOD: From a total of 1,970 suicides that occurred in New York City from 1990 to 1992, 1,635 cases that had a complete toxicologic analysis and an injury-death interval of 48 hours or less were assessed at autopsy for the presence of commonly prescribed antidepressants and neuroleptics. RESULTS: Prescription psychotropic medications were detected in only 16.4% (N = 268) of the suicide victims studied. Demographic factors associated with use of these drugs included female gender and white race. Poisoning accounted for 17.9% (N = 293) of all suicides studied, but antidepressants or neuroleptics were detected in less than half of these victims. Among all suicide victims in whom an antidepressant or neuroleptic was detected, almost half had used lethal methods other than poisoning. CONCLUSIONS: In this study, most individuals who committed suicide in New York City were not taking prescription psychotropic medications at the time of their death and either were not receiving pharmacotherapy or were noncompliant.

Adult↗

PubMed1995

Cocaine, opiates, and ethanol in homicides in New York City: 1990 and 1991.

Studies using medical examiner cases are useful in monitoring drug use in special populations. This study assesses the presence of cocaine and its metabolite, benzoylecgonine (BE), opiates and ethanol in all homicide victims who were injured and who survived two hours or less after injury in 1990 and 1991 in New York City. There were 2824 homicides in the study period and cocaine and/or BE were found in 884 (31.3%) of cases. In over half of the cases positive for cocaine/BE, ethanol or opiates were found. African-Americans and Latinos were much more likely than whites or Asians to be positive for cocaine/BE. There were no differences between men and women in regard to being positive for cocaine/BE. Cocaine/BE was most frequently identified among victims 25 to 44 years of age. Males were more likely to be positive for ethanol. There were no differences among age groups or ethnic groups in regard to ethanol except for a very low ethanol incidence among Asians. Victims positive for cocaine/BE were more likely to be killed with firearms in open places. The percentage of victims positive for cocaine/BE remains approximately that found by other studies in the late 1980s, however, the percentage of opiate-positive homicides seems to be increasing. Opiates usually were found with cocaine/BE. Two-thirds of the cocaine and/or BE positive cases had cocaine present, thus they were under the influence of the drug at the time they were injured. The authors discuss how the use of cocaine, ethanol and opiates may be related to one's becoming a homicide victim.

Adolescent↗

PubMed1994

Homicide in New York City. Cocaine use and firearms.

OBJECTIVE: To determine differences between racial/ethnic groups in overall rates of death by homicide, proportion of firearm homicides, and the use of cocaine prior to death. DESIGN: Descriptive epidemiologic survey of a complete 2-year sample of homicides. SETTING: New York City, NY (population 7,322,564). SUBJECTS: All residents (N = 4298) of New York City who were victims of homicide during 1990 and 1991. MAIN OUTCOME MEASURES: Using medical examiner data, age- and gender-specific rates of homicide were calculated for African Americans, Latinos, and whites. Separate logistic regression analyses were conducted to examine the association between demographic variables and both recent cocaine use and firearm-related homicides. RESULTS: Young African-American and Latino men were more likely to be victims of homicide than all other demographic groups. Approximately three fourths of all homicides involved firearms. In the subset of homicide victims dying within 48 hours (n = 3890), 31.0% were positive for cocaine metabolites. African Americans (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1), Latinos (OR, 1.4; 95% CI, 1.1 to 1.9), and victims 25 through 34 years of age (OR, 2.9; 95% CI, 2.5 to 3.5) and 35 through 44 years of age (OR, 2.7; 95% CI, 2.2 to 3.4) were more likely to be positive for cocaine metabolites than other groups. Young males and females were equally likely to have used cocaine before death. Victims 15 through 24 years of age were more likely than other age groups to be killed by a firearm. African Americans (OR, 1.7; 95% CI, 1.3 to 2.3), Latinos (OR, 1.5; 95% CI, 1.2 to 2.0), and Asians (OR, 2.2; 95% CI, 1.4 to 3.6) were more likely than whites to be killed by a firearm. Men (OR, 4.8; 95% CI, 4.0 to 5.9) were more likely than women to be killed by a firearm. There was no association between having used cocaine before death and being killed by a firearm. CONCLUSIONS: The high rates of death by homicide among young African Americans and Latinos may be due to the increased involvement with both cocaine use and firearms. New efforts must be made to decrease cocaine use and firearm availability.

Adolescent↗

PubMed1994

Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages.

The relative phagocytosis and intracellular fate of Mycobacterium tuberculosis (MTB) (H37Ra) in human alveolar macrophages (AM) and their precursors blood monocytes (MN) was investigated. Uptake of MTB by MN and AM was confirmed by electron microscopy. At an infection ratio of 100:1 (MTB:target cell), the percentage of infected AM and the number of MTB per AM was > MN (p < 0.001, p < 0.0001, respectively). Uptake of MTB was increased by increasing concentrations of serum and decreased in the presence of heat-inactivated serum. Among complement receptors (CR) CR1, CR3, and CR4, the major CR mediating uptake of MTB by MN were CR1 and CR3, whereas for AM, CR4 was the major CR. When MN and AM were infected with MTB and cultured for up to 7 days, AM limited intracellular growth of MTB more effectively than MN as determined by a CFU assay. MTB stimulated production of TNF-alpha by mononuclear phagocytes and by AM > MN (p < 0.007). Pentoxifylline inhibited TNF-alpha production by mononuclear phagocytes and concurrently increased MTB growth (AM > MN). A polyclonal neutralizing antibody to TNF-alpha also increased MTB growth in AM. Thus, AM are more efficient in phagocytosis of MTB than MN, and uptake is mediated through CR4 to a greater extent than CR1 or CR3. The slowed replication of MTB in AM is associated with an increase in TNF-alpha production, and intracellular growth is promoted by pentoxifylline and neutralizing antibody to TNF-alpha. These data suggest that AM may play a prominent and efficient role in the primary defense of the lung in tuberculosis through CR-mediated uptake, predominantly CR4, and TNF-alpha-mediated killing of MTB.

Cells, Cultured↗