Risk Assessment in Immunotoxicology II. Relationships between Immune and Host Resistance Tests

Luster, Michael I.; Portier, Christopher J.; Pait, D. Gayla; Rosenthal, Gary J.; Germolec, Dori R.; Corsini, Emanuela; Blaylock, Benny L.; Pollock, Pam; Kouchi, Yasuhide; Craig, William A.; White, Kimber L.; Munson, Albert E.; Comment, Christine E.

doi:10.1006/faat.1993.1074

Cited by 307 publications

(163 citation statements)

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“…The latter situation is analogous to the use of a higher challenge dose of live bacteria in a model that does not require immunization. Thus, the present results with streptococcus group B seem consistent with the more extensive study of Luster et al (6), indicating increased sensitivity to suppressed host resistance with increasing challenge doses of microorganisms or cancer cells. However, our results with L. monocytogenes suggest that this may not be the case for all pathogens or all experimental systems.…”

Section: Discussionsupporting

confidence: 93%

“…Thus, multivariate analysis seems preferable to using individual variables in single regression analyses. This latter approach yields very low r 2 values for most immune function parameters (6), and none of these simple linear models explained a greater amount of the variance in host resistance or predicted more outcomes correctly than noted in this work for multivariate methods. However, it is interesting that the only factor in our streptococcus group B model that contributed significantly to the model contained three variables (number of blood lymphocytes and number of two cellular subpopulations in the peritoneal cavity) that one would not have expected to be the most important in resistance to streptococcus group B (Tables V and VI).…”

Section: Discussioncontrasting

confidence: 56%

“…It is clear that drastic suppression of one or more immune functions decreases host resistance to infection (4) or cancer (5). However, it is not presently possible, even in animal models (6), to predict the cumulative effects of several smaller changes in immune system parameters on host resistance.…”

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confidence: 99%

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Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

Keil¹,

Luebke

Pruett

2001

The Journal of Immunology

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Although reductionist experimental designs are excellent for identifying cells, molecules, or functions involved in resistance to particular microbes or cancer cells, they do not provide an integrated, quantitative view of immune function. In the present study, mice were treated with either dexamethasone (DEX) or cyclosporin A (CyA), and immune function and host resistance were evaluated. Multivariate statistical methods were used to describe the relative importance of a broad range of immunological parameters for host resistance in mice treated with various dosages of DEX. Multiple regression and logistic regression analysis indicated that changes in 24 immunological parameters explained a substantial portion of the changes in resistance to B16F10 tumor cells or streptococcus group B. However, at least 40% of the change in host resistance remained unexplained. DEX at all dosages substantially suppressed numerous relevant immunological parameters, but significantly decreased resistance to Listeria monocytogenes only at the highest dosage. In contrast, CyA substantially decreased resistance to L. monocytogenes at dosages that caused relatively minor suppression of just a few immunological parameters (unfortunately, CyA data and host resistance data for L. monocytogenes were not suitable for multivariate analysis). These results illustrate that mathematical models can be used to explain changes in host resistance on the basis of changes in immune parameters, and that moderate changes in relevant immunological parameters may not produce the types of changes in host resistance expected on the basis of results from reductionist experimental designs.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 56%

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Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

Keil¹,

Luebke

Pruett

2001

The Journal of Immunology

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“…Traditional methods for toxicological assessment have implicated the immune system as a frequent target organ of toxic insult following exposure to certain drugs or environmental chemicals. A tiered approach, a screening battery, for characterizing potential immunotoxic compounds have been developed and validated in laboratory animals (Dean et al, 1985;Luster et al, 1988Luster et al, , 1992Luster et al, , 1993. These reports indicated that the highest associations with immunotoxicity were the T-dependent antibody response to SRBCs (78%) and the lymphocyte subpopulation analysis (83%) as determined by surface marker expression, and that the performances of only two or three immune tests are sufficient to predict immunotoxic compounds in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…Because the AFC assay is the most sensitive indicator of the host's ability to mount an antibody response to a specific antigen (Luster et al, 1993), the splenic antibody response to SRBCs was chosen. In the present study, gross indicators of immunotoxicity, such as changes in lymphoid organ weights, were not affected following FPP-3 treatment, whereas the number of AFC was significantly reduced at the highest dose of FPP-3 (Table I and Fig.…”

Section: Discussionmentioning

confidence: 99%

Immunotoxicological Investigation of 1-furan-2-yl-3-pyridin-2-yl-propenone in Female BALB/c Mice

Jeon¹,

Kim²,

Lee³

et al. 2009

Biomolecules and Therapeutics

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-1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-α. In the present study, adverse effects of FPP-3 on immune functions were determined in female BALB/c mice. When mice were administered orally with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days, FPP-3 suppressed the number of antibody-forming cells and reduced thymus weight at 500 mg/kg. In addition, FPP-3 administered mice exhibited reduced splenic cellularity and numbers of splenocyte subsets, such as CD3 These results suggested that FPP-3 at 500 mg/kg might be immunotoxic, and that FPP-3-induced immunotoxicity might be mediated, at least in part, through the inhibition of cytokine production, such as IL-4.

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Differential modulation of natural and adaptive immunity in fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields

Tremblay

Houde

Mercier

et al. 1996

Bioelectromagnetics

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Two separate, independent experiments were conducted to evaluate the effect of 60 Hz linearly polarized, sinusoidal, continuous‐wave magnetic fields (MFs) on immune system performances in rats born and raised under these fields. Each experiment lasted for 6 weeks. A total of 96 animals, divided into groups of eight animals each, was exposed for 20 h/day to MFs of different intensities, i.e., sham (<0.02 μT) and 2, 20, 200, and 2000 μT. Another group of animals, which was housed in a separate room, served as cage controls (CC). These animals were exposed to ambient MFs of <0.02 μT. The following immune responses were evaluated in both experiments: total T and B cells; CD4+ and CD8+ subpopulation and natural killer (NK) cell activity in splenic lymphocytes; hydrogen peroxide (H2O2), nitrous oxide (NO), and tumor necrosis factor (TNF) production by peritoneal macrophages. Our results show that a 6 week exposure to MFs induced a significant decrease in the number of CD5+, CD4+, and CD8+ populations. These changes were even more significant in rats that were exposed to fields of 2000 μT. A lower, although significant, decrease in the CD5+ population was also observed in animals that were exposed to fields of 200 μT. Linear regression analysis demonstrated a dose effect with MF intensity. B lymphocyte (Ig+ cell) populations also showed a 12% decrease (P < .05) in the groups that were exposed to fields of 20 and 200 μT. However, these results were not significant, and no relation with MF intensities could be demonstrated. In contrast, evaluation of splenic NK cell activity revealed a 50% increase (P < .05) in animals that were exposed to fields of 2000 μT. No significant results were obtained from the evaluation of TNF activity and NO secretion in peritoneal macrophages. Phorbol 12‐myristate 13‐acetate (PMA)‐stimulated and net H2O2 productions for a minor subpopulation of peritoneal cells showed positive dose‐response correlations by linear regression analysis. Taken together, our results suggest that an in vivo exposure of rats for 6 weeks to 60 Hz MFs can induce significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose‐dependent fashion. © 1996 Wiley‐Liss, Inc.

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Risk Assessment in Immunotoxicology II. Relationships between Immune and Host Resistance Tests

Cited by 307 publications

References 0 publications

Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

Immunotoxicological Investigation of 1-furan-2-yl-3-pyridin-2-yl-propenone in Female BALB/c Mice

Differential modulation of natural and adaptive immunity in fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields

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