Reducing Mortality in
            <i>Salmonella enterica</i>
            Serovar Typhimurium-Infected Mice with a Tripeptidic Serum Fraction

Parker, Todd; Willeford, Kenneth O.; Parker, Suzanne L.; Buddington, Karyl K.

doi:10.1128/aac;46.6.1971-1973.2002

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…In a recent study, Willeford et al [2000] established that a fraction of caprine serum, substantially free of immunoglobulins, improved the survival of chickens infected with Pasteurella multocida when given 24 h prior to the bacterial challenge. Similar results were noted by Parker et al [2002] in mice challenged with Salmonella typhimurium. In this report, we show that the serum fraction, now termed Innate Immune Regulatory Factor (IIRF), induces a protective immune response via an NK cell-dependent pathway.…”

Section: Introductionsupporting

confidence: 90%

“…Previous studies with IIRF demonstrated an ability to protect against lethal bacterial challenges such as Salmonella typhimurium [Parker et al, 2002] and Pasteurella multocida [Willeford et al, 2000]. IIRF was most effective when given 24 h prior to challenge.…”

Section: Nk Cells Mediate An Iirf-induced Immune Response Against Bacmentioning

confidence: 91%

“…The major components of IIRF consist of a small degree of albumen (which lacks biological activity [Parker et al, 2002]) and several peptidic components. The peptidic components of IIRF were separated by analytical C-18 reverse phase chromatography, which confirmed the presence of three peaks (Fig.…”

Section: Innate Immune Regulatory Factor (Iirf) Preparationmentioning

confidence: 99%

“…We examined whether NK cells participated in IIRF-induced events. To test this possibility, a previously established bacterial model [Parker et al, 2002] was used. Control or IIRF treated mice were depleted (495% according to the manufacturer's design) of NK cells by injection of anti-asialo GM-1 and then challenged with a potentially lethal dose of S. typhimurium.…”

Section: Nk Cells Mediate An Iirf-induced Immune Response Against Bacmentioning

confidence: 99%

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An innate immune regulatory factor (IIRF) prevents tumorogenesis in a murine melanoma challenge model

et al. 2005

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Biological response modifiers (BRMs) are a family of compounds defined as agents or approaches that modify the host response to pathogens. A serum-derived small peptide, termed Innate Immune Regulatory Factor (IIRF), stimulates the immune response through a natural killer cell-dependent pathway in mice. Ten days after administering a lethal dose of Salmonella typhimurium, 85% of control mice died. No difference was observed between control and mice depleted of natural killer cells and administered IIRF. However, only 30% of natural killer cell intact mice treated with IIRF died by day 10, indicating the critical role of natural killer cells in an IIRF-induced immune response. The protective effects of IIRF were also examined in a natural killer cell-dependent melanoma model. Female B6C3F1 mice were injected with 8 Â 10 5 B16F10 melanoma cells/mouse. Lung samples obtained from control and IIRF treated mice (5 mg on day À1) were analyzed using computerized imaging. Tumor morphometric analysis showed that 53710% of the lung surface from control mice was cancerous. Prophylactic administration of IIRF lowered this value to 3079%, a statistically significant decrease (P ¼ 0.014). When this experiment was repeated with 1 Â 10 5 cells, the number of melanoma nodules on the lung surface could be established through microscopic examination. Control mice (n ¼ 10) had an average of 8877 tumor nodules, whereas IIRF-treated mice (n ¼ 8) had 44712 tumor nodules, a twofold reduction (P ¼ 0.0036). These results suggest that IIRF is a BRM with therapeutic potential for cancer treatment. Drug Dev Res 64: 213-219, 2005.

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Section: Introductionsupporting

confidence: 90%

Section: Nk Cells Mediate An Iirf-induced Immune Response Against Bacmentioning

confidence: 91%

Section: Innate Immune Regulatory Factor (Iirf) Preparationmentioning

confidence: 99%

Section: Nk Cells Mediate An Iirf-induced Immune Response Against Bacmentioning

confidence: 99%

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An innate immune regulatory factor (IIRF) prevents tumorogenesis in a murine melanoma challenge model

et al. 2005

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“…Thacker and colleagues (34) reported the isolation, structure elucidation, and synthesis of an NME, 1-peptidyl-2-arachidonoyl-3-stearoyl-sn-glyderide, derived from a caprine serum fraction similar to that which had been previously reported (2,20,29,30). The chemical structure is shown in Fig.…”

mentioning

confidence: 97%

NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs

Thacker

Balin

Appelt

et al. 2012

Antimicrob Agents Chemother

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We describe the molecular mode of action and pharmacodynamics of a new molecular entity (NME) that induces the NLRP3 inflammasome-mediated innate immune response. This innate response reduces the pathogen load in an experimentally induced methicillin-resistant Staphylococcos aureus infection, enhances survival in an experimentally induced Gram-negative bacteremia, and overrides the escape mechanism of an obligate intracellular pathogen, viz. Chlamydia pneumoniae. Furthermore, the NME is more effective than standard-of-care antibiotic therapy in a clinically established multifactorial bacterial infection. Analysis of transcriptional regulation of inflammasome signaling genes and innate/adaptive immune genes revealed consistent and significant host changes responsible for the improved outcomes in these infections. These studies pave the way for the development of first-in-class drugs that enhance inflammasome-mediated pathogen clearance and identify the NLRP3 inflammasome as a drug target to address the global problem of emerging new infectious diseases and the reemergence of old diseases in an antibiotic-resistant form.

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Interleukin-6 expression in response to innate immune regulatory factor stimulation

Parker

Cheng

Willeford

et al. 2011

Biomedicine & Pharmacotherapy

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Reducing Mortality in Salmonella enterica Serovar Typhimurium-Infected Mice with a Tripeptidic Serum Fraction

Cited by 5 publications

References 8 publications

An innate immune regulatory factor (IIRF) prevents tumorogenesis in a murine melanoma challenge model

An innate immune regulatory factor (IIRF) prevents tumorogenesis in a murine melanoma challenge model

NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs

Interleukin-6 expression in response to innate immune regulatory factor stimulation

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