HDFx: A Novel Immunomodulator and Potential Superbug Super - Warrior for Hospitalized Patients and Battlefield Casualties
1 Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
2 Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
3 The Center for Cardiovascular and Muscle Research, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
4 The School of Graduate Studies in Molecular and Cellular Science, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
5 Bio-Defense Systems, Inc, Rockville Centre, New York, USA.
6 Orient Biomedica, Inc, Estero, Florida, USA.
Dr. Burton M. Altura,
Department of Physiology and Pharmacology,
The School of Graduate Studies in Molecular and Cellular Science, Downstate Medical Center, Brooklyn, New York, USA.
Received: October 09, 2016; Published: October 15, 2016
Citation: Altura BM (2016) HDFx: A Novel Immunomodulator and Potential Superbug Super - Warrior for Hospitalized Patients and Battlefield Casualties. Int J Vaccines Res. 3(1e),1-3.
Copyright: Altura BM© 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Over the past decade, a disturbing trend in antimicrobial resistance of both gram negative and gram-positive pathogens and "superbugs" has seriously complicated the treatment of many immuno-compromised, hospitalized patients [1-8]. Too this major problem must be added the numerous hospitalizations and deaths from contaminated meats, poultry, vegetables, seafoods, and dairy products [9-11]. Government resources, worldwide, are being overstretched and often remain powerless to combat these assaults on our populations. Almost one million people per year are killed by bacteria and "superbugs" due to antimicrobial resistance. If we add the untold millions per year who are dying from drug-resistant tuberculosis in Africa and India , the number of deaths becomes staggering. By about 2075, the number of people dying from drug-resistant infections could reach in excess of 35 million per year. Each year, in the USA alone, more than 150 million prescriptions are written, 60% of which are for antibiotics. Of these, it has been estimated that 50 million of these costly prescriptions are probably unnecessary . Added to this is the ever-growing and soaring worldwide use of antibiotics in agriculture. How much of this indiscriminate use of antibiotics is contributing to the ever-growing resistance of pathogens to antibiotics noted above?
Our laboratories have been working on a new approach to develop host-defense factors that stimulate various arms of the innate and adaptive immune systems. To this end, we have discovered a new host-defense factor, termed "HDFx", that is a conserved protein found in mice, rats, guinea-pigs, rabbits, and sub-human primates [13-16]. We assume it is also present in humans since it is a conserved molecule. More than 135 years ago, Elie Metchnikoff, the great father of immunology, hypothesized that the body , under stressful circumstances, might produce powerful immuno-stimulants which perforce would act on different arms of the innate immune system and serve to protect against major insults and diseases . Metchnikoff's early studies pointed to the important contributions of macrophages and phagocytic leukocytes to natural (innate) resistance against pathogenic bacteria and viruses. Over the past 30-40 years, considerable evidence has accumulated to support a strong relationship between the functional (physiological) state of the microcirculation, macrophages-phagocytes, natural killer (NK) cells, the reticuloendothelial system, and "pit cells" in the liver to host defense and resistance to pathogens, trauma, circulatory shock and combined injuries [18-25].
Recent studies from our laboratories have clearly shown that HDFx is protective(to diferent degrees) against a variety of systemic bodily insults ranging from hemorrhage, trauma, endotoxins, a variety of lethal bacteria(e.g., E.coli, S.enteriditis, C. welchii), combined injuries, centripetal forces, and septic shock [13-16]. A unique attribute of HDFx is that it can accelerate wound healing , and it has protective qualities even in diseases such as nonalcoholic steatohepatitis (NASH) which often results in liver carcinomas . We have suggested that HDFx might be useful in the treatment and amelioration of hemorrhagic fever viruses .
In the past few years, many hospitalized patients have died of common and once treatable bacterial diseases, such as pneumonia, and blood (septic) or urinary tract infections [1-8]. Today, it is difficult to undertake major surgical procedures or chemotherapy without antibiotics, as patients die afterwards from infections [1-8]. Gram-negative superbugs seem to be the major culprits in most of these patient deaths [1-8]. Gram-negative bacteria appear to be more difficult to kill than gram-positive bacteria because they are protected by "double membranes". So, in order to kill the gram-negative bacteria, most of the approaches have been to design antibiotics to penetrate these membrane barriers. In our opinion, another likely approach would be to engulf the bacteria and digest them within macrophages, Kupffer cells, phagocytic leukocytes, platelets, and NK cells. But, for the latter to occur, we believe that the microcirculation to key organs, namely the liver, spleen , and lung must perforce have optimal capillary blood flow and distribution. Therefore, an ideal drug or therapeutic molecule would be one that could stimulate multiple arms of the innate immune system coupled to modulation of microcirculatory blood flows in the aforementioned key organ systems. So far, HDFx appears to be the only molecule that combines these qualities and demonstrates therapeutic attributes against several classes of bacterial "superbugs" [13-16].
For millennia, diseases and and non-combat injuries have resulted in the vast majority of lost combat days in the battlefield. During the Mexican (1845-1848) and Spanish-American (1898) wars disease-related deaths outnumbered battlefield deaths by seven to one . During recent wars in Vietnam (1969-1975), Iraq (2001-present and Afghanistan (2001-present), American and UN coalitin forces have continued to demonstrate a mounting number of diverse diseases in battlefield troops which have taken great tolls in morbidity and mortality despite improved transportation, treatment, hygiene, and new advances in management [27, 28]. Many of the infections produced by a variety of microorganisms, parasites, and vectors such as pneumonia, Q fever, brucellosis, tuberculosis, and malaria have become antibiotic-and drugresistant and exhibit superimposed infections with Acinetobacter species [27-30]. In addition, many of the warfighters exhibit gastroenteritis, prolonged diarrhea, and drug-resistant respiratory infections. Inadequate treatment often results in loss of body parts, amputations, and disfigurements. Many of these men and women on return to the USA , and other native countries, require prolonged hospitalization, and treatment often at great cost without restoration to normalcy. The uniqueness of HDFx to accelerate wound healing  and promote tissue regeneration  should greatly aid treatment and recovery of our warfighters.
We believe the approaches outlined in the above, using HDFx or its derivatives, could be the ideal drug(s) to pretreat all patients scheduled for major surgeries and given post-surgery to prevent lethal infections by a variety of "superbugs".
A major objective of our group is to secure adequate funding to elucidate the complete, complex molecular structure of HDFx and then via genetic engineering to produce large quantities of HDFx for further testing in human subjects and animals under diverse pathophysiological and battlefield conditions, including infections produced by "superbugs".
Some of the original studies and thoughts needed for the discovery of HDFx and reviewed, above, were initiated while the author was at New York University School of Medicine and The Albert Einstein College of Medicine of Yeshiva University. Some of the original studies reviewed , above, were supported, in part, by unrestricted grants from several pharmaceutical companies (CIBA-GEIGY Pharmaceuticals, Sandoz Pharmaceuticals, Bayer Pharmaceuticals) and anonymous donors. The author is indebted to many colleagues, over many years, who helped make our studies and background experiments possible: C. Thaw, E.W. Burton, J.Hanley, C.Parillo, A. Carella, and A. Gebrewold. The author is also grateful for the many discussions with Professor Bella T. Altura.
- Gaynes E, Edwards R (2005) Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 41(6): 948-954.
- Blossom DB, McDonald LC (2007) The challenges posed by reemerging Clostridium difficile infection. Clin Infect Dis. 45(2): 222-227.
- Burton DC, Edwards JR, Horan TC, Jernigan JA, Fridkin SK (2009) Methicillin- resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units. JAMA. 301: 727-736.
- Lee JH, Jeong SH, Cha SS, Lee SH (2009) New disturbing trend in antimicrobial resistance of gram-negative pathogens. PloS Pathog. 5(3): e1000221.
- Kuehn BM (2007) antibiotic-resistant "Superbugs" may be transmitted from animals to humans. JAMA. 298(18): 2125-2126.
- Holden MTG, Hauser H, Sanders M, Ngo TH, Cheverach I, et al., (2009) Rapid evolution of virulence and drug-resistance in emerging pathogen Streptococcus suis. PloS One. 4(7): e6072.
- Marston HD, Dixon DM, Knisely JM, Palmore TN, Fauci AS (2016) Antimicrobial resistance. JAMA. 316(11): 1193-1204.
- Zignol M, Dean AS, Falzom D, van Gemert W, Wright A, et al., (2016) Twenty years of global surveillance of anttuberculosis- drug resistance. N Engl J Med. 375(11): 1081-1089.
- Anonymous (2009) Preliminary foodnet data on the incidence of infection with pathogens transmitted commonly through food-10 states, 2008. MMWR. 158(13): 333-337.
- Maki DG (2009) Coming to grips with foodborne infection-Peanut, butter, pepper, and Nationwide Salmonella outbreaks. N Engl J Med. 360(10): 949-953.
- Schiller LR (2009) Infectious disease: A germy world-foodborne infections in 2009. Nature Rev Gastroenterol Hepatol. 6(4): 197-198.
- Tierno PM (2001) The Secret Life of Gems: Observations and lessons from a Microbe Hunter. Pocket Books, New York.
- Altura BM, Gebrewold A, Carella A (2009) A novel biologic immunomodulator, HDFx, protects against lethal hemorrhage, endotoxins and traumatic injury: potential relevance to emerging diseases. Int J Clin Exp Med. 2(3): 266-279.
- Altura BM, Carella A, Gebrewold A (2011) HDFx: a novel biologic immunomodulator is therapeutically-effective in hemorrhagic and intestinalischemic shock: Importance of microcirculatory-immunological interactions and their potential implications for the warfighter and disaster victims. Int J Clin Exp Med. 4(4): 331-340.
- Altura BM, Carella, Gebrewold A (2012) HDFx: a novel biologic immunomodulator accelerates wound healing and is suggestive of unique regenerative powers: potential implications for the warfighter and disaster victims. Int J Clin Exp Med. 5(4): 289-295.
- Altura BM, Gebrewold A, Carella A (2016) HDFx: A recently discovered biologic and its potential use in prevention and treatment of hemorrhagic fever viruses and antibiotic- resistant superbugs. J Hematol Thromboembolic Dis. 4(4): 100252.
- Metchnikoff E (1884) Untersuchung ueber die intracellulare Verdauung beiwirbellosen Thieren . Arbeiten aus dem Zoologischen Institut zu Wien. 5(2): 141-168.
- Altura BM (1980) Recent progress in pathophysiology of shock: Reticuloendothelial and neuro-endocrine stimulation. J Clin Anesth. 4: 745.
- Altura BM (1980) Reticuloendothelial cells and host defense . Adv Microcirc. 9: 252-294.
- Van der Meer JW (1981) Pathophysiology of the Reticuloendothelial System, Raven Press, New York. Immunol Today. 3(11): 320.
- Ulevitch RJ, Mathison JC, Tobias PS (1983) The role of the macrophage in host response to bacterial endotoxins. In : The Pathophysiology of Combined Injury and Shock. 5: 87-92.
- Angele MK, Chaudry IH (2005) Surgical trauma and immunosupression: Pathophysiology and potential immunomodulatory approaches. Langebecks Arch Surg. 390(4): 334-341.
- Majno G, Joris I (2004) Cells, Tissues and Diseases. ( 2nd Edn),Oxford University Press, New York.
- Caligiuri MA (2008) Human natural killer cells. Blood. 112(3): 461-469.
- Murphy K, Weaver C (2016) Janeway's Immunology . (9th Edn), Garland Science, New York.
- Altura BM, Gebrewold A, Carella A, Altura BT (2016) HDFx; Potential new treatment and prophylactic against nonalcoholic steatohepatitis (NASH) and subsequent hepatocellular carcinomas: Is hypomagnesemia a complication of the disease? J Alcoholism and Drug Depend , in press.
- Murray CK, Hinkle MK, Yun HC (2008) History of infections associated with combat-related injuries. J Trauma. 64(3): 221-231.
- Eardley WGP, Brown KV, Bonner AD, Green AD, Clasper JC (2011) Infection in conflict wounded. Phil Trans R Soc. 366(1562): 204-218.
- Aronson NE, Sanders JW, Moran KA (2006) In harm's way: Infections in deployed American military forces. Clin Infect Dis. 43(8): 1045-1051.
- Sanders JW, Putnam SD, Frankart C, Frenck RW, Monteville MR, et al., (2005) Impact of illness and non-combat injury during operations in Iraqi Freedom and Enduring Freedom (Afghanistan). Am J Trop Med Hyg. 73(4): 713-719.