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Smith EM, Blalock JE. Human leukocyte production of corticotropin and endorphin-like substances: Association with leukocyte interferon. Proc. Natl. Acad. Sci. USA 1981;78:7530-7534

J. Edwin Blalock received his B.S. and Ph.D. degrees in 1971 and 1976 from the University of Florida. After one-year postdoctoral training at the University of Texas Medical Branch, Galveston, he joined the faculty in 1977 and earned the title of Professor of Microbiology in 1984. Dr. Blalock joined the University of Alabama at Birmingham (UAB) faculty in 1986 as Professor of Physiology and Biophysics. Then, he entered the UAB Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine in 2009. Blalock is internationally recognized for his research in neuroimmunology, rational drug design, as well as the role of inflammation in chronic lung diseases. Due to his expertise on rational drug design, he joined the team of CuraVac, a Belgian pharmaceutical company, that used Blalock’s “vaccine production technique” in order to find medicaments to treat autoimmune diseases like myasthenia gravis.

Concerning his partner, Eric M. Smith, there is insufficient data on the internet to report on his full CV. However, at the time they met, he was a medical scientist at the Department of Microbiology, University of Texas Medical Branch, Galveston. Eric M. Smith is a renowned researcher in the field of neuroendocrine immunology. Together with J. Edwin Blalock, he published more than 40 papers on these subjects.

The discovery of Blalock and Smith

In the late 1970s, Blalock was interested in antiviral activities of interferons, and he observed that these lymphokines had “hormone-like activities” and hormones were shown to have cell-specific interferon-like activities (1). In a paper of 1980 (2), Blalock and Smith showed “strong antigenic relatedness among human leukocyte interferon, ACTH, and endorphins, implying that there are underlying structural similarities.” Later, IFN-α was cloned and analysis of the DNA showed that there were no ACTH sequences in the protein. Thus, structural relatedness was not the key solution to the problem. It seemed that ACTH was co-produced with IFN-α and present in the preparation at the same time. Indeed, the important paper showed that affinity purification and separation on SDS–polyacrylamide gels demonstrated that a 22-Kd biosynthetic intermediate of pro-opiomelanocortin (POMC, precursor of ACTH) had been co-purified with the 23-Kd form of IFN-α (3). Subsequent studies established that leukocyte ACTH was biologically active and antigenically identical to the pituitary peptide. Thus, leukocytes produce peptide hormones.

In this decisive work on leukocyte hormone production, the authors wrote: “The detection of ACTH and endorphin-like materials in lymphocytes demonstrates that the immune system can produce substances that are related to known polypeptide hormones and that are capable of signaling the neuroendocrine system.”

Based on these results, Blalock later developed the concept of the sixth sense (4,5). Through the sharing of ligands and receptors the immune system could serve as a sixth sense to detect things the body cannot otherwise hear, see, smell, taste or touch.

In one form or the other, the existence of hormone production in immune cells stood the test of time and some relevant experiments have also been published in Neuroimmunomodulation (6-11).

References

1. Blalock JE, Stanton JD. Common pathways of interferon and hormonal action. Nature. 1980;283(5745):406-408
2. Blalock JE, Smith EM. Human leukocyte interferon: structural and biological relatedness to adrenocorticotropic hormone and endorphins. Proc Natl Acad Sci U S A. 1980;77(10):5972-5974
3. Smith EM, Blalock JE. Human Leukocyte production of corticotropin and endorphin-like substances: Association with leukocyte interferon. Proc. Natl. Acad. Sci. USA 1981;78:7530-7534
4. Blalock JE. The syntax of immune-neuroendocrine communication. Immunol Today. 1994;15:504-511
5. Blalock JE, Smith EM. Conceptual development of the immune system as a sixth sense. Brain Behav Immun. 2007;21:23-33
6. Liu Q, Arkins S, Biragyn A, Minshall C, Parnet P, Dantzer R, Kelley KW. Competitive reverse transcriptase-polymerase chain reaction using a synthetic internal RNA standard to quantitate transcripts for leukocyte-derived hormones. Neuroimmunomodulation 1994;1:33-41
7. Rohn WM, Weigent DA. Cloning and nucleotide sequencing of rat lymphocyte growth hormone cDNA. Neuroimmunomodulation. 1995;2:108-114
8. Throsby M, Pleau J, Dardenne M, Homo-Delarche F. Thymic expression of the pancreatic endocrine hormones. Neuroimmunomodulation 1999;6:108-114
9. Weigent DA, Vines CR, Long JC, Blalock JE, Elton TS. Characterization of the promoter-directing expression of growth hormone in a monocyte cell line. Neuroimmunomodulation 2000;7:126-134
10. Arnold RE, Weigent DA. The inhibition of apoptosis in EL4 lymphoma cells overexpressing growth hormone. Neuroimmunomodulation 2004;11(3):149-159
11. Markus RP, Ferreira ZS, Fernandes PA, Cecon E. The immune-pineal axis: a shuttle between endocrine and paracrine melatonin sources. Neuroimmunomodulation 2007;14:126-133

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